University of California San Francisco
…A Health Sciences Campus
DEPARTMENT OF RADIOLOGY
I M AG ES
2002
University of Cali...
Contributing Writers:
Ronald L. Arenson, MD; Michael Barnes; Corby Dale, PhD, MPH; William P. Dillon, MD; Chris
Dowd, MD; ...
1
Table of Contents
Letter from the Chairman
2
Clinical and Research News
4 Recent Advances in the CT Diagnosis of Acute C...
2
Dear Friends,
We have completed another very successful year!
Our new faculty members are listed in the Departmental Upd...
3
research facility will include a 3T magnet and a number of animal imaging devices. The major
emphasis of this research f...
4
Stroke is the third leading cause of death in the United
States, and the leading cause of adult disability. Stroke affec...
5
scanning. While this compromises temporal resolution
somewhat, perfusion parameters can nevertheless be de-
rived from t...
6
C l i n i c a l a n d R e s e a r c h N e w s
patients treated in comparison to
those without treatment. UCSF is
conside...
7
Diagnosing Cancer With Lasers
Author: Michael Barnes
An innovative University of California program is
bringing together...
8
C l i n i c a l a n d R e s e a r c h N e w s
task to develop fluorescent markers that will glow when ex-
cited by the l...
9
With the aging population of the United States, degen-
erative diseases affecting the joints, spine and other skeletal
s...
10
C l i n i c a l a n d R e s e a r c h N e w s
quantitative in-
formation re-
garding these
factors above to
best aid in...
11
be the first step in attempting to design effective surgical
interventions and therapeutic regimens to promote repair
a...
12
C l i n i c a l a n d R e s e a r c h N e w s
Outcomes research focuses on
the results of health care decisions.
It add...
13
chorionic villus sampling] performed to diagnose these
cases). Areas that used serum biochemistry or nuchal trans-
luce...
14
Surveillance, Epidemiology, and End Results (SEER) Program
of the National Cancer Institute (NCI). These data include
s...
15
Medical diagnoses commonly rely on assessment of
both the functional status and the anatomical condition of
the patient...
16
C l i n i c a l a n d R e s e a r c h N e w s
accounts for differences in scanner geometry and image for-
mat (e.g., 12...
17
talented individuals in the Department of Radiology who have
been responsible for the growth and development of dual-
m...
18
C l i n i c a l a n d R e s e a r c h N e w s
The Dynamic Neuroimaging Laboratory (DNL), located
on the Parnassus campu...
19
EEG/MEG results from the transmembrane currents of
neocortical pyramidal neurons, whose apical dendrites lie
along the ...
20
brain function in terms of underlying neuronal constitu-
ents and their synaptic interactions, but realize that a purel...
21
Evolving Applications on the Interventional X/MR System
Authors: David Saloner, PhD William P. Dillon, MD Chris Dowd, M...
22
C l i n i c a l a n d R e s e a r c h N e w s
quantitative measure of the extent to which occlusion of a
specific arter...
23
was achieved using an interactive viewer with a true tempo-
ral resolution of 5 fps and a reconstruction rate of 10 fps...
24
On September 11, a day that many spent in prayer
and meditation, 75 people came to hear Robert Lull, MD,
speak on “Is N...
2525
Effects estimated for a 1 kiloton nuclear weapon in San Francisco with detonation at
the Transamerica building as hyp...
26
Over the last three years, there has been a dramatic
expansion in the number of students in the joint UCSF/UCB
Bioengin...
27
The Clinical PACS group had an eventful year. The good
news is that the new version of software for our commercial
PACS...
28
Equipment Changes and Challenges
Author: Robert G. Gould, ScD
TheDepartmentofRadiologyhascompletedseveralprojects
this ...
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I M A G ES

  1. 1. University of California San Francisco …A Health Sciences Campus DEPARTMENT OF RADIOLOGY I M AG ES 2002 University of California San Francisco
  2. 2. Contributing Writers: Ronald L. Arenson, MD; Michael Barnes; Corby Dale, PhD, MPH; William P. Dillon, MD; Chris Dowd, MD; Thomas Ferree, PhD; Jennifer Gennari Shepherd; Charles A. Gooding, MD; Roy L. Gordon, MD; Michael B. Gotway, MD; Robert G. Gould, ScD; Van Halbach, MD, Bruce Hasegawa, PhD; Randall A. Hawkins, MD, PhD; Randall T. Higashida, MD; Charles B. Higgins, MD; Morgan Hough; Tracy Luks, PhD; Alastair Martin, PhD; Hideyo Minagi, MD; Tym Peters; David Saloner, PhD; Kendrick Shunk, MD; Sharmila Majumdar, PhD; Sarah J. Nelson, PhD; Phil Reser; Hanh Ryan; Maythem Saeed, PhD; Greg Simpson, PhD; Rebecca Smith-Bindman, MD; Richard A. Sollitto, MD; Oliver Weber, PhD; Mark W. Wilson, MD. Design: Lisa Krieshok Editorial Assistance: Jennifer Gennari Shepherd Editorial Coordinator: Ramona Lipske Printing: University of California Printing Services About the cover: Courtesy of Gary R. Caputo, MD, associate professor in residence, Nuclear Medicine Electron beam CT coronary angiogram of a 72-year-old woman status post four vessel saphenous vein bypass grafting to the right coronary artery, the obtuse marginal branch of the circumflex, and a sequential graft to the left anterior descending coronary artery and its diagonal branch. The patient had refused evaluation of her coronary artery disease by conventional cardiac catheterization. A widely patent right coronary graft, and the sequential left anterior descending graft with a moderate proximal stenosis, are demonstrated. The third vein graft was not visualized and was presumed to be occluded proximally. Three clips are seen in the ascending aorta, one of which may mark the site of the origin of the occluded vein graft. The patient was imaged using a GE Imatron scanner and the study was volume rendered on an Aquarius TeraRecon workstation.
  3. 3. 1 Table of Contents Letter from the Chairman 2 Clinical and Research News 4 Recent Advances in the CT Diagnosis of Acute Cerebral Infarction and Hemorrhage 7 Diagnosing Cancer with Lasers 9 Morphological and Functional Musculoskeletal Imaging 12 Outcomes Research and Evidenced-Based Radiology 15 Dual-Modality Imaging with SPECT/CT 18 Imaging Brain Dynamics 21 Evolving Applications on the Interventional X/MR System 24 Nuclear Terrorism: What You Should Know 26 Development of Bioengineering at UCSF 27 Clinical PACS Group New Facilities and Technology 28 Equipment Changes and Challenges Departmental Update 29 Olympic X-ray: Close-up for a UCSF Radiologist 30 Former Resident Endows Neuroradiology Chair 30 Lecture Honors T. Hans Newton, MD 31 The Margulis Society 33 Donor’s List 34 Residency Program 35 First-Year Radiology Residents 2002-2003 39 Second-Fourth Year Radiology Residents 39 Nuclear Medicine Residents 39 Clinical Fellows in Radiology 40 2002 Radiology and Nuclear Medicine Resident Graduates 41 New Faculty Appointments 44 Retired in 2002 44 Faculty on the Move 45 Faculty Roster 48 Honors and Awards 49 Alumni News 50 In Memoriam 51 Radiology Learning Center 53 Radiology Postgraduate Education 53 Resident Receives Inaugural Renee Sauers Award 54 Radiology CME Offerings in 2003 55 Online Continuing Education Courses Introduced 56 Business Office Welcomes New Staff 57 Radiology Outreach Foundation Radiology Research 59 Research Directions and Key Recent Publications 77 Grants 78 Patents 79 Research Laboratories
  4. 4. 2 Dear Friends, We have completed another very successful year! Our new faculty members are listed in the Departmental Update section. We continue to attract the most outstanding junior faculty. Jessica Leung, MD, will be returning to us in Novem- ber after a sojourn at the Brigham to work in Mammography and to lead our Women’s Imaging program. It is hard to imagine that we could recruit better residents than we have already, but I am completely convinced that we attract the very best in the country. We continue to beat out every institution for the highest choices on our match list. Likewise, in contrast to programs all around the country, we continue to fill our fellowships with outstanding candidates. I am proud that we have increased the percentages of women and minorities as well. Eugene Morita, MD, retired this past year after many years of devoted service in Nuclear Medicine, primarily at Mt. Zion Hospital. Fortunately, we were able to convince him to return part-time, much to the delight of our referring colleagues at Mt. Zion. I am very sorry to an- nounce that David Avrin, MD, PhD, has moved to Utah. At least, he did so for the right reasons: To be close to his family as they pursue their dreams on the ski slopes. The University of Utah probably doesn’t yet realize the gift that has come their way! The Department has continued to experience significant growth in clinical work and re- search funding. We have experienced the most growth in CT and MR but all areas have shown increases. Our research faculty continue to add to their grant portfolios in spite of our severe space shortages. This year we completed an external review with flying colors! External reviews are con- ducted by leaders in the field from other institutions. Our Department was the first at UCSF to undergo such an evaluation, probably because I was the one who instigated the idea. The re- viewers praised most aspects of the Department and its leadership but did make a number of important suggestions, which are now being adopted. The materials that were pulled together for this review are available on our website: http://www.radiology.ucsf.edu. Feel free to browse the details; I am sure you will agree that they demonstrate the health and strength of our Department. The report was somewhat critical of the Medical Center’s support for the Department, but I am now satisfied that the Medical Center leadership is providing all the support that is reason- able at this time. The Medical Center is doing much better financially and it appears to be well on its way to the financial stability needed to fund a new hospital in a decade or so. Planning for the new hospital is currently underway, including selection of the optimal site for one or two hospitals. Much of this year’s capital budget was devoted to re-opening Mt. Zion as an overflow in-patient facility as well as for information systems. The Department is moving ahead with a number of important expansion projects, both clinical and research. Near Mission Bay, we are finalizing our choice of buildings in which we are renting around 50,000 sq. ft. for both research and clinical space. The clinical space will house a number of MR and CT scanners as well as a PET scanner to be installed in the future. The L e t t e r F r o m t h e C h a i r m a n
  5. 5. 3 research facility will include a 3T magnet and a number of animal imaging devices. The major emphasis of this research facility will be molecular and functional imaging, but it will also house informatics researchers and a variety of other laboratories. A cyclotron will also be located at this site to serve all of our PET scanners as well as others in the community. We hope to open this facility before the end of this academic year. Our CME programs remain quite strong. We continue to provide CME to more radiologists than any other institution. We have embarked on our new web-based CME and have already signed on a number of radiologists. It’s always a pleasure to see our alumni at our CME courses. Thanks for attending so frequently! Lee Gately, our departmental administrator, left us at the end of last year to return to Bos- ton to be with her family. I am extremely pleased to announce that we have recruited Cathy Garzio to take her place. I had to persuade Cathy, a former administrator at the UCSF Cancer Center, to return to work after staying home with her young children for a while. The Margulis Society continues to support many programs in the Department, especially associated with the residency program. We are slowly building an endowment that one day will be the Society’s greatest legacy. I am very pleased to announce to you the generous contribution from Beth Guillaumin, MD, to create an endowed professorship in Neuroradiology. With this wonderful gift in hand, we are beginning the process of identifying a can- didate to fill the chair. We are most grateful to Beth and her husband, Charles Perrell, for their generosity and commitment. I am also very happy to announce that the Dean’s Office has agreed to $250,000 matching funds to add to the Minagi Endowed Professor- ship. We have just begun recruiting to fill that important position at the San Francisco General Hospital. Now that we have completed the external review, my stewardship review is underway. Feel free to send letters of support! And please stop by at our reception on Sunday night of the RSNA and visit our new booth close to Publisher’s Row. See you there! Sincerely, Ronald L. Arenson, MD 3
  6. 6. 4 Stroke is the third leading cause of death in the United States, and the leading cause of adult disability. Stroke affects more than 750,000 persons each year, and there are now more than 4 million survivors with major disability as a result of a stroke. In the emerging era of thrombolytic therapy for stroke, the prompt identification of a patient with (or without) an acute cerebral perfusion deficit or cerebral hemorrhage is criti- cal if appropriate and effective therapy is to be administered (or withheld) in a timely fashion. Recent advances in multi-detector CT (MDCT) tech- nology now permit rapid acquisition of data during infu- sion of intravenous contrast, revealing information about the perfusion status of regional areas of the brain, as well as arterial anatomy. CT perfusion is performed by acquiring a series of 20 scans at two 20 mm slice locations before and during the passage of a bolus of 40 cc of con- trast. A series of parametric images are constructed that reflect the mean transit time (MTT) of contrast through the brain, the relative cere- bral blood volume (rCBV) and rela- tive cerebral blood flow (rCBF) (Fig- ures 1-4). These perfusion maps have been shown to add sensitivity to the presence of cerebral ischemia (see “Dynamic CT perfusion to assess the effect of carotid revascularization in chronic cerebral ischemia” Roberts et al in Am J Neuroradiol 2000; 21(2):421-5) and can predict in many instances the viability of tissue. One disadvantage of the CT perfusion technique is the limited anatomical coverage of the single slice data acquisi- tion. We have introduced a technique to expand the ana- tomical coverage of a dynamic CT perfusion technique by toggling the table between two locations during dynamic C l i n i c a l a n d R e s e a r c h N e w s Recent Advances in the CT Diagnosis of Acute Cerebral Infarction and Hemorrhage Authors: William P. Dillon, MD Randall T. Higashida, MD Figure 1: CT perfusion in a patient with left hemiparesis of 2-hour duration. Non-contrast CT is unremarkable, with the exception of a dense vessel in the sylvian cistern, suggesting a hyperdense embolus (arrow). Figure 2B: Relative cerebral blood flow map shows slightly elevated r CBV in the right hemisphere, indicating collateral flow. This is a good sign that indicates adequate perfusion, at present. It suggests, however, that there might be tissue at risk of infarction. Figures 2A-2B: CT perfusion maps derived from a 40 cc bolus of contrast at two slice locations. Shown is one 10mm location. 2A. Mean transit time map. The map demonstrates a delay in mean transit time of contrast to the right middle cerebral territory (arrow).
  7. 7. 5 scanning. While this compromises temporal resolution somewhat, perfusion parameters can nevertheless be de- rived from the dynamic contrast-enhanced CT data over a larger area of the brain. (See “Multisection dynamic CT perfusion for acute cerebral ischemia: The “toggling-table” technique” Roberts et al in Am J Neuroradiol 2001; 22(6):1077-80.) Imaging data may also be acquired over the length of a vessel during contrast injection and por- trayed as 3-D reconstructed images of the arterial or venous anatomy (Figures 5, 6). While both CTA and MRA can give similar results, CT is generally more available than MR, is more time efficient, and safer in many ways for the critically ill patient. CT, however, is limited by beam hardening artifacts and by superimposed dental amalgam and heavy arte- rial calcification. At UCSF, we have implemented an acute stroke protocol consisting of non-contrast CT fol- lowed by CT perfusion and CT angiography of the extracranial and intracranial vasculature. This ro- bust protocol is performed in less than 20 min- utes, and requires a total contrast dose of 140 cc. Over 500 patients have been scanned using this protocol. CT angiography rapidly evaluates the ce- rebral circulation, identifying critical stenosis of the extracranial circulation as well as embolic oc- clusion of the intracranial circulation (Figure 3). Using these new tools, an assessment of relative cerebral perfusion as well as the anatomic source of these ischemic deficits can be rapidly derived. Other applications of CT perfusion and CTA include the identification of cerebral aneurysms (Figure 6) and as- sessment of vasospasm from subarachnoid hemorrhage. CTA has been shown to be as sensitive as angiography for aneu- rysms larger than 3 mm in size and can in some instances obviate angiography in patients presenting with acute sub- arachnoid hemorrhage, even in those with small aneurysms of less than 5 mm in size (see “Detection and characteriza- tion of very small cerebral aneurysms by using 2D and 3D Helical CT Angiography” Villablanca et al, in Am J Neuroradiol 2002; 21(2):421-5). Therapeutic Options Once a person has been diagnosed with an acute is- chemic stroke, treatment depends upon the time of clinical presentation and the degree of tissue involved. Currently, patients with stroke onset of less than 3 hours duration, with less than 1/3 of the affected cortical tissue involved, are candidates for intravenous tissue plasminogen activator (tPA), which acts to dissolve the blood clot. This has been shown to improve good outcomes in more than 30% of Figure 3: MIP slab from a CT angiography study demonstrates an embolus to an M2 branch of the right middle cerebral artery, accounting for the delayed mean transit time and hyperdense vessel on non-contrast CT. Figure 4: 2-hour history of aphasia. (A) Non contrast CT is normal, however MTT (B) and CBV (C) maps show a perfusion deficit in the left posterior frontal lobe. The reduction in CBV is a poor prognostic sign, and indeed this patient sustained an infarction in the same distribution.
  8. 8. 6 C l i n i c a l a n d R e s e a r c h N e w s patients treated in comparison to those without treatment. UCSF is considered one of the major centers specializing in the rapid diagnosis and treatment of patients with stroke, and has a “stroke neurology” team in place to rapidly assess the patients in the Emergency Room, and to ad- minister this treatment. For patients who present after 3 hours, other treatment options are available. The UCSF Interventional Neurovascular Radiology Division provides 24/7 coverage to manage pa- tients not eligible for IV t-PA. Newer therapies, which in- volve placement of microcatheters directly into the blood clots into the brain and then giving thrombolytic drugs di- rectly at the site of blood vessel blockage, have also been shown to significantly improve blood flow to the brain tis- sue and improve outcomes. In addition, for patients diagnosed with a cerebral an- eurysm, the UCSF Interventional Neuroradiology group has also pioneered many of the minimally in- vasive treatment techniques. It is now possible to treat both ruptured and unruptured cerebral aneurysms using platinum microcoils placed into the an- eurysm for occlu- sion. This acts to block blood flow to the aneurysm, and therefore obviates the need for patients to undergo tradi- tional surgical cran- iotomy and clipping of their aneurysm. T h e U C S F neuroradiology, i n t e r v e n t i o n a l neuroradiology, and neurology groups have recently ana- lyzed their outcomes from endovascular Figure 5: 3-D reconstruction of CTA in another patient with calcified atherosclerosis of the carotid bifurcation (workstation provided by Terarecon, Inc.). Figure 6: 3-D model from a CT angiogram of the circle of Willis in a patient presenting with subarachnoid hemorrhage. CTA shows aneurysms arising from the right middle cerebral, left middle cerebral, and anterior communicating arteries (arrows). coiling of aneurysms compared to surgery. There were sig- nificant better overall outcomes for patients, with less in- hospital morbidity and mortality, less length of stay, and re- duced overall costs associated with these newer, less inva- sive techniques. As further improvements in the rapid diagnosis and treatments are made, for both ischemic and hemorrhagic stroke, we believe that overall patient outcomes will also continue to improve.
  9. 9. 7 Diagnosing Cancer With Lasers Author: Michael Barnes An innovative University of California program is bringing together researchers from UC campuses and na- tional laboratories to collaborate on pathbreaking research projects. With funding from the Campus-Laboratory Col- laborations Program, UC San Francisco radiologist Robert Brasch and Lawrence Livermore National Laboratory laser scientist Stavros Demos are building new tools to diagnose breast cancer. Their technique for optical tissue imaging is based on the ability of infrared laser light to penetrate three to four centimeters into the human body, deep enough to illumi- nate tumors in the breast. If you hold a flashlight tight against the palm of your hand in a dark room, you can see a faint red glow through the back of your hand. The tissues in your hand block most of the colors except the reds. If you could put on a pair of nightvision goggles that intensify only certain wavelengths of infrared light, your hand would appear to be translucent. Instead of using a flashlight, Livermore’s Demos has designed an infrared laser to illuminate tumors within hu- man tissue. “The development of high-quality nonlinear optical materials has led to lasers that can be tuned through a wide spectral range,” explains Demos. Demos’s laser starts with a pulse of near-infrared light at a wavelength of 1064 nanometers (billionths of a meter) that passes through a series of specialized crystals. By varying the angles of the crystals, Demos can select a range of light from 670 nm (a deep red) to 950 nm (near-infrared). By comparison, visible light occupies that portion of the electromagnetic spectrum from violet, at a wavelength of about 400 nm, to red, at about 700 nm. “Our laser system can be tuned from the red to the infrared spectral region to cover the entire ‘optical win- dow’ in the near-infrared suitable for optical imaging of tissues,” says Demos. The near-infrared is suitable for op- tical imaging because light with wavelengths shorter than 600 nm gets absorbed by hemoglobin and other related molecules, while infrared light with wavelengths longer than 1500 nm gets absorbed by water. This is why the light passing through your hand appears so red – all the other visible light has been filtered out, except for a narrow band of barely visible deep red light. To illuminate tumors within human tissue, the laser Demos has designed must operate in the range of 800 to 900 nm. Once tissue is illuminated with infrared laser light, the next task is to discriminate a tumor from surround- ing tissue. This is where UCSF’s Brasch comes in. Brasch, a specialist in pediatric radiology and the director of the UCSF Contrast Media Laboratory, works on developing agents that can be swallowed or injected to highlight tissues for imaging by CAT scans, MRIs and X-rays. In his collaboration with Demos, it will be Brasch’s “Hey, can I play video games on this thing?” LLNL laser scientist Stavros Demos and UCSF radiologist Robert Brasch share a chuckle as Demos demonstrates the prototype laser he designed. UCSF attracts the best minds from all over the world, and the Brasch and Demos research group is no exception. It includes (L to R) post-graduate researchers Laure Fournier (France), Vincenzo Lucidi (Italy), Yanjun Fu (China), and Victor Novikov (Ukraine).
  10. 10. 8 C l i n i c a l a n d R e s e a r c h N e w s task to develop fluorescent markers that will glow when ex- cited by the laser light. The glow will be detected by a spe- cialized digital camera with filters that will record only the light emitted by the fluorescent markers. Optical tissue imaging has several advantages over X-rays, CAT scans and MRIs. Unlike X-rays, it does not in- volve radiation. The laser also will be cheaper and much smaller than MRI or CAT scan machines and capable of be- ing used at the bedside. Most important, optical imaging is highly sensitive and capable of producing very specific mo- lecular information about a tumor. Marker molecules that fluoresce or glow under infra- red light can be designed to attach only to particular sites on cancer cells. With a set of fluorescent markers designed to highlight different biological processes within a tumor, a mix of markers could be administered, and the tumor in- vestigated with different frequencies of laser light. A unique cancer profile could be developed to help design an optimal strategy to fight a particular tumor. “There is not just a single disease called breast cancer,” say Brasch. “Breast cancer comes in many different forms and variations. One of our best options for the future is to choose treatments on the basis of biology for each tumor. We are creating imaging tools to characterize individual can- cers and thus to individualize treatment for each patient,” Brasch adds. Judging response to treatment is another area where diagnostics could be improved by optical imaging. The cur- rent state of the art is to provide chemotherapy or radiation therapy and then to wait six to eight weeks to see if a patient’s tumors are shrinking. With optical tissue imaging, tracing the effect of therapy on the biological processes of a tumor could begin the day after therapy is administered. The patient’s treatment plan then could be updated quickly based upon the tumor’s reaction to therapy. The main drawback to optical imaging is its inability to penetrate more than three to four centimeters inside the body. However, lights and cameras are already placed on catheters for many medical tests. If lasers and digital cameras can be placed on the end of fiber-optic catheters, optical diagnostics can be used to probe the condition of arteries inside the heart, or tumors in internal organs. Like many of the pathbreaking technologies supported by the Campus-Laboratory Collaborations Program, optical imaging with fluorescent probes may be too new and un- tested to attract grant funding from traditional sources. The beauty of the UC collaborations program is that it provides seed money for early-stage research. Successful results then can be used to attract funding from the National Institutes of Health and from other research funders. “Although our research is at a very early stage, we’re excited about the possibilities,” states Brasch. “The Cam- pus-Laboratory Collaborations Program has brought to- gether two scientists with complementary skills who other- wise might not have had the chance to work together.” A tumor in a laboratory rat is illuminated by fluorescent probes and infrared laser light. Demos’s hand illuminated by the red light of his tunable laser.
  11. 11. 9 With the aging population of the United States, degen- erative diseases affecting the joints, spine and other skeletal sites are growing to be a major source of morbidity, declin- ing quality of life, and are taking a serious financial toll on society. Imaging has made a tremendous impact in diagnos- tic procedures, in surgical planning, and guided surgical applications. However, beyond anatomical and subjective depictions of anatomy, quantitative, morphological and func- tional musculoskeletal imaging methods are still underutilized. Over the last two years, there has been a fo- cused attempt to increase collaborative efforts and address the development of quantitative musculoskeletal imaging in the Department of Radiology at the University of Califor- nia, San Francisco. Spurred on by a Bioengineering Research Partnership Grant from the National Institutes of Aging, par- ticipants from UCSF (Sharmila Majumdar, PhD, Lynne Steinbach, MD, and Cynthia Chin, MD, in Radiology; Jef- frey Lotz, PhD, and Michael Ries, MD, in Orthopedic Sur- gery; Karen King, PhD, in Medicine), Lawrence Berkeley National Laboratories (Thomas Budinger, MD, PhD) and industrial partners have focused on the systematic study of the morphology and function of the musculoskeletal sys- tem in disease and health. The team effort utilizes the strength of each individual partner at the inception and throughout the design of tech- nological advances. This sets a format for interaction, which prevents the isolated development of tools and techniques that are irrelevant and unrealistic in the clinic, or need elabo- rate modifications and redesign at the time of clinical utili- zation and commercialization. In the development of these imaging techniques, the inclusion of corporate partners es- tablishes the pathway for utilizing already established pro- Morphological and Functional Musculoskeletal Imaging Author: Sharmila Majumdar, PhD totypes, use of corpo- rate resources, rapid standardization, testing and clinical dissemina- tion of the techniques. While the long- term objective of this consortium is to under- stand the link between morphology, function and clinical symptoms in the musculoskeletal system, an immediate objective has been to develop, implement and optimize novel non-invasive imaging methods (magnetic resonance imaging [MRI] and positron emission tomography [PET], infra-red imaging, and micro-computed tomography) that will allow us to depict the musculoskeletal system, quantitate morphol- ogy, function, provide unique 3-D visualization and graphic representations of function and morphology. In particular, the goal has been to leverage the quantitative aspects of im- aging to further complement the characterization of degen- erative knee, and the spine and enhance the clinical utility of imaging. Disorders of the Spine Disorders of the spine have a tremendous impact on society, both physically, through the morbidity of afflicted individuals, and financially, through lost productivity and increased health care costs. Back pain is the second leading cause for ambulatory care in the United States and direct medical costs for this condition are estimated at over $20 billion per year. ‘Medical back problems’ comprised the sec- ond most common medical diagnosis-related group for all hospital discharges in 1987, following only normal child- birth. Despite the significance of this problem, the etiology of symptoms is diverse and unclear in many patients, and consequently there are few reliable methods by which to prospectively determine the appropriate course of patient care (i.e. conservative management or surgery). Three principal causes for patient complaints are: ab- normal motion-instability; tissue inflammation; and forami- nal stenosis or narrowing of the foraminal space, which may result in nerve compression. With these factors in mind, the last two years have led to the development and research for the optimal imaging modality which would contain Figure 1. Images of the lumbar spine showing a giant plasma cell tumor and the use of novel diffusion weighted imaging sequences. Figure 2. Three dimensional computed tomography (CT) images of the lumbar vertebrae showing the metrics used for assessing vertebral narrowing and stenosis, often an indicator of lower back pain. 9
  12. 12. 10 C l i n i c a l a n d R e s e a r c h N e w s quantitative in- formation re- garding these factors above to best aid in estab- lishing the patient’s diagno- sis. Optimizing the use of novel MR imaging, such as line scan diffusion techniques, Chin, David Newitt, MD, and Bashir Taoli, MD, are exploring the possibility of improved quanti- tative characterization of spinal conditions. As seen in Fig- ure 1, a fat suppressed image in a patient with a plasma cell tumor shows a bright region, and a corresponding diffusion image to the right shows a significant dark tumor region. Images such as these, that reflect differences in tissue water diffusion, a characteristic of tissue composition and biochem- istry, provide a means of quantitatively describing patho- logical changes. Computed tomography methods, using newly installed multi-detector scanners exploring age-related narrowing of the spinal canal and narrowing of the foraminal space, are also under investigation. In Figure 2, Thomas Lang, PhD, has generated a three-dimensional rendering of a vertebral body from a stack of computed tomography images. The figure shows some of the metrics that can be measured us- ing such images. Using these metrics, we have found that subjects who had reported symptoms such as pain, numb- ness, and weakness in the legs, tended to have lower bone density but larger vertebral size than normal subjects. Con- sistent with expectations, the spinal canal area tends to be smaller in subjects with symptoms, and the ratio of verte- bral cross-sectional area to spinal canal area is larger. There was a tendency for symptomatic subjects to have more osteophytes and more narrowing of the lateral recess than the normal subjects, as well as potentially a trend for symp- tomatic subjects to have more narrowing of the foramina. In collaboration with UC Berkeley’s Jitendra Malik, PhD, and Sergie Belonghi, PhD, bioengineering graduate student Julio Carballido has developed methods for segmenting the vertebral bodies as seen in Figure 3. This combination of state- of-the-art MR methods with CT imaging and computerized image analysis holds tremendous potential for studying lower back pain, degeneration of the spine, and age-related spinal stenosis. Proposed studies using PET (Budinger) will further enhance the research in this area, bringing molecular imag- ing into the realm of the clinic in the foreseeable future. Degenerative Diseases of the Knee Joint Joint pain and physical impairment are responsible for extensive use of medical and surgical resources in the United States. The important tissues of the joint are the bones, the synovial membrane, the cartilage on the surfaces of the ar- ticulating bones, which provide a low coefficient of friction surface allowing smooth joint motion, and the ligaments and tendons, which attach the articulating surfaces or are attached to these surfaces. Osteoarthritis (OA) and related disorders accounted for 85% of all total knee replacements and total costs for knee and hip replacements are well over $300 million. The course of OA is challenging to describe. It is a het- erogeneous and multifactorial disease characterized by the progressive loss of cartilage and the development of altered joint alignment, as well as changes in the adjoining bone. The integrity of the articular cartilage and the inter-relation- ship between the bone and adjoining cartilage is very im- portant in maintaining joint stability and preventing joint degeneration and an impairment of function. Physicians seek safe and effective ways to treat OA and musculoskeletal dis- ability. To assess therapy, diagnostic tools that quantitatively measure progression, degeneration and yet correlate with clinical measures, are essential. A better understanding of the etiology, biochemical changes, metabolic changes and kinematics or motion studies of the degenerative joint should Figure 3. Segmentation of the MR images of the lumbar spine, the overlay in pink (right) shows the area not categorized in the vertebral body cluster. Figure 4. High-resolution MR image of the articular cartilage (top left, bright signal is cartilage), and trabecular bone in the tibia (top right). The image on the top right shows the bone marrow as a bright signal and the trabecular bone as a dark network. The images on the bottom are three dimensional renderings of the segmented cartilage images as shown on the top left. The bottom left shows the femoral cartilage in a normal subject, whereas the bottom right is the femoral cartilage showing degeneration in an osteoarthritic subject.
  13. 13. 11 be the first step in attempting to design effective surgical interventions and therapeutic regimens to promote repair after injury and prevent joint failure and degeneration. With these goals in mind, high-resolution magnetic reso- nance images have been developed to image the cartilage as well as the bone in the knee joint. As seen in Figure 4, the high signal cartilage can be defined, and its volume and thick- ness not only can be visualized, as seen in the figure, but also quantified. The relationship between bone changes and carti- lage changes in osteoarthritis remains a major question, and unraveling the timing of these changes will have a major im- pact on understanding the pathophysiology of OA as well as devising treatments. Using the images depicting the fine bone network as seen in Figure 4, the link between such cartilage- bone interactions may be unearthed. OA is not a disease of static joints, but one that is me- diated by biomechanical loading as in gait, and understand- ing the alignment of the bones and meniscus is of some importance in assessing the status of the joint. Previous stud- ies of knee motion have been limited by invasiveness, two- dimensionality, accuracy of marker positioning, or lack of physiologic weight bearing. Using a novel device developed by Vikas Patel, MD, an orthopedic surgery resident, three- dimensional, MR studies that replicated load bearing in the magnet were undertaken. Tibio-femoral and patello- femoral motion was studied, first in normals and then in subjects with instabilities and osteoarthritis. Images were obtained in different positions of flexion and extension, as shown in Figure 4. The relative motion of the bones (patella and femur in Figure 5), the translation, and the area of con- tact, was quantified. MR images of cartilage also provide quantitative infor- mation pertaining to relaxation times such as T2, which depend on the collagen content and chemical composition of articular cartilage. A bioengineering graduate student in Majumdar’s laboratory, Srinka Ghosh, worked in close col- laboration with Michael Ries, MD, of Orthopedic Surgery and obtained specimens of the cartilage from subjects un- dergoing total knee replacement. Longer T2 values are ac- companied by a histological confirmation of disorientation of the cartilage fibers, fibrillation and fissures. Following up on this tissue characterization work, Tim Dunn, a sec- ond year bioengineering graduate student, has developed a method for mapping T2 changes in human sub- jects. The T2 values ob- tained in the cartilage are expressed as a ratio of the T2 values in healthy sub- jects, overlaid as a color map on the MR images (Figure 6). The shades of blue and purple are close to a value of 0, and corre- spond to the healthy range of T2 values; yellow and red re- flect higher values corresponding to subjects with severe osteoarthritis. In an effort to complement the imaging studies, King, in the Department of Medicine, has been collaborating with investigators in Radiology, and analyzing serum samples from the subjects who have undergone MR scanning. She has used ELISA analysis to quantify molecular markers for joint degeneration (Cartilage oligomeric matrix protein [COMP] and Serum CILP, a cartilage-specific protein, also from the extracellular matrix). Initial results demonstrate that as total cartilage volume decreases, serum COMP and CILP increase. These data also show that a moderate cor- relation exists between a subject’s serum COMP level, as measured by ELISA, and the amount of cartilage in medial tibia, as measured by MRI. The investment of $4.5 million made by the National Institutes of Aging for the Bioengineering Research Partner- ship for musculoskeletal imaging involves combining a num- ber of state-of-the-art methods to characterize the joint, and spine develop imaging, as well as serum biomarkers. This consortium of specialists, collaborating across disciplines, are working toward developing techniques that ultimately will be used to assess the clinical status of the subject more effectively. Figure 5. Three dimensional images showing the femur and patellar during kinematic imaging (MR) showing the relative positions of the bone during extension and flexion, and positions in between. Figure 6. MR images through the knee of a normal volunteer (left) and a subject with severe osteoarthritis (right). On the gray scale image is the overlay of T2 maps showing lower values of T2 in blue, and higher values in yellow.
  14. 14. 12 C l i n i c a l a n d R e s e a r c h N e w s Outcomes research focuses on the results of health care decisions. It addresses how interventions and treatments impact important pa- tient outcomes, such as morbidity, mortality, and quality of life, rather than more immediate and isolated results, such as whether a lesion is detected or whether a tumor shrinks following treatment. Put simply, outcomes research tries to ascertain how patients are helped and harmed by what we do to them, so that we, and they, can make more informed decisions. This focus on outcomes is relatively new in the field of radiology, but it is clearly just as important to know how a new test affects patient outcomes, as it is to know whether that test improves diagnostic accuracy. For example, while a screening test such as spiral CT may detect lung cancer cases prior to the time they would have become symptom- atic, it may potentially harm patients if, through false posi- tives, it leads to large numbers of unnecessary open lung biopsies in patients without cancer, or if it has no impact on those with cancer because the detected cancers would not have caused symptoms in the patient’s lifetime. Outcomes research requires thinking about radiology as it affects patients in the context of their disease, other diagnostic tests, and treatment interventions. Typically, out- comes research requires large numbers of subjects and dif- ferent types of study designs from those common in radiol- ogy research. The members of UCSF’s Radiology Outcomes Research Laboratory (RORL) bring diversity of experience and training, not only in medicine and radiology, but also in epidemiology, biostatistics, demography, anthropology, pub- lic administration and policy, and population health. We also actively collaborate with investigators from the UCSF De- partments of Medicine, Obstetrics and Gynecology, Pediat- rics, and Epidemiology and Biostatistics. Under the direction of Rebecca Smith-Bindman, MD, current RORL research concentrates on the impact of radio- logical imaging on women’s health. Recent studies have ad- dressed: (1) the use of prenatal ultrasound for diagnosis of birth defects, chromosomal abnormalities, and reproductive outcomes; and (2) screening mammography, including screening strategies and programs, physician predictors of mammographic accuracy, and optimal ages for stopping mammographic screening. Ultrasound for the Detection of Down Syndrome Fetuses Second trimester ultrasound is widely used to detect Down Syndrome (DS) fetuses, but the accuracy of this method is unknown. The RORL recently published a sys- tematic review in the Journal of the American Medical Asso- ciation that found the existing published literature does not support the use of prenatal ultrasound as a screening test for DS. The review suggested that in otherwise low-risk women, if ultrasound is used as a screening test, it will lead to more losses of healthy fetuses as an expected complica- tion risk of amniocenteses (triggered by the false positive ultrasound) than cases of DS detected. To empirically estimate the performance of prenatal ultrasound as a screening test for DS and other chromo- somal abnormalities, the RORL is currently collaborating with the California Maternal Serum Expanded AFP Program, a state-mandated DS screening program, to prospectively evaluate the role of ultrasound in women who participate in this program. We have recently collected the ultrasound re- sults on the cohort of 19,694 women who participated in this program between 1999-2000 by using a standardized data form administered in 29 sites in California. The ultra- sound results will be compared with serum biochemical screening results and birth outcomes to determine if ultra- sound adds additional information to that obtained by se- rum testing alone. Related studies using these data will study the impact of ultrasound on the detection of a broad range of birth defects, as this sample also includes large numbers of cases of neural tube defects (n=250), severe growth restriction (>1000), and other defects. Also using these data, the RORL will investi- gate associations between physician characteristics, such as specialty (radiology versus perinatology) and training, and the accuracy of interpretation of prenatal ultrasound. These studies will provide information that women and clinicians can use when deciding about prenatal testing. The RORL recently completed an analysis to determine if patient outcomes in the United Kingdom vary by the types of methods used to screen for DS. This study of all of En- gland and Wales for ten years, including 5,980,519 preg- nant women, 335,184 invasive prenatal tests, and 12,047 DS diagnoses, compared population outcomes for local ar- eas that predominantly screened for DS via (a) serum bio- chemistry, (b) first trimester nuchal translucency, and (c) maternal age. Our main outcomes measures were effective- ness (percentage of cases prenatally diagnosed) and efficiency (number of invasive prenatal tests [amniocentesis and Outcomes Research and Evidenced-Based Radiology Author: Rebecca Smith-Bindman, MD Rebecca Smith-Bindman, MD
  15. 15. 13 chorionic villus sampling] performed to diagnose these cases). Areas that used serum biochemistry or nuchal trans- lucency screening detected 50% more DS cases before birth than areas that used advanced maternal age as their domi- nant method of screening (52% and 49% vs. 35% respec- tively) and had lower live-born DS rates. Screening with serum biochemistry or nuchal translucency also was asso- ciated with the performance of fewer invasive procedures to diagnose each DS case than screening based on maternal age (62 and 61 vs. 90 invasive procedures per DS case de- tected respectively). Thus, screening for DS based on serum biochemistry or nuchal translucency is more effective and efficient than screening based on advanced maternal age. Surprisingly, most professional guidelines in the U.S. (American College of Obstetrics and Gynecology, American College of Medical Genetics, and U.S. Preventive Task Force, etc.) continue to endorse advanced maternal age screening for DS. The RORL has started a similar study in the U.S. to evaluate amniocentesis rates, prenatal DS detection rates, and prevalence of live-born DS rates. They will collect data from hundreds of cytogenetic laboratories and U.S. State Birth Defect Registries to try to better understand current practices related to prenatal screening for birth defects, as well as differences that are seen in actual clinical practice based on the screening methods used. Screening Mammography Although randomized trials of screening mammogra- phy have shown a 30% reduction in breast cancer mortality among screened women, women older than age 74 were not included in any of the trials. Thus, the optimal age at which to stop mammographic screening remains unknown. The RORL published an analysis in the American Journal of Medi- cine that evaluated the effectiveness of screening mammog- raphy in women ages 70-79, among approximately 700,000 women in California, in whom 6,000 were diagnosed with breast cancer. They found a substantial benefit of mammog- raphy in older women, but raised questions to the degree to which older women were being over-diagnosed with breast cancer, analogous to prostate cancer in elderly men. A number of studies in the RORL research projects are evaluating the impact of screening mammography on pa- tient outcomes in elderly women (such as stage of disease at diagnosis, breast cancer treatments, and breast cancer and total mortality). These studies will use national Medicare claims data linked to national tumor registry data from the Dr. Smith-Bindman confers with statisticians Bill Chu, PhD and Chris Quale, PhD.
  16. 16. 14 Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). These data include screening mammography utilization and outcomes on 70,000 women diagnosed with breast cancer from 1991–1996 from across the U.S., and their age-matched controls, and it is hoped these studies will provide important in- formation for physicians and patients to use when deciding about what age to cease mammographic screening. As part of this analysis, we are analyzing differences in outcomes of screening mammography based on patient demographics and co-morbidity to determine which women have the greatest potential benefit of undergoing mammography. A separate study will focus on causes of racial disparity (higher rates of breast cancer mortality in the African-American population) in breast cancer mortality. Despite the clear benefits of screening mammography, its accuracy is only modest; it produces large numbers of false positive examinations (5-20%) leading to high rates of biopsy, and misses 10-20% of true cancers. Additionally, wide differences across physicians have been reported. Several studies in the RORL are analyzing physician predictors of the accuracy of interpretation of screening and diagnostic mammography. One study uses data from the Breast Can- cer Surveillance Consortium (BCSC), an NCI-funded con- sortium of mammography registries in seven U.S. states. These data describing the prospective interpretation of over 1,000,000 mammograms, including approximately 5,000 diagnosed with breast cancer, have been linked with tumor registry data and data from the American Medical Associa- tion Master File on physician characteristics. The RORL is currently evaluating physician predictors of mammographic accuracy (e.g., annual volume of interpretation and years since training) among the approximately 300 physicians who interpreted these examinations to try to better understand how to improve the accuracy of mammography. The RORL is nearing completion of a comparative study of differences in the accuracy of screening mammography, and methods used to diagnose cancer, between the United States and the United Kingdom. This collaborative effort between the RORL, the BCSC, the Centers for Disease Con- trol and Prevention, and the U.K. National Health Services Breast Screening Program, includes nearly 6 million mammograms obtained between 1996–1999. Smith- Bindman recently pre- sented the results of this analysis at a Global Sum- mit on Mammography held in Milan, Italy. The dramatic results found that recall and open sur- gical biopsy rates were two-fold higher in the U.S. compared to the U.K., without significant differences in the cancer detection rates. Efforts to improve mammographic screening in the U.S. clearly should aim at lowering recall rates without substantially reducing cancer detection rates. Summary The tremendous upsurge of diagnostic testing over the last decade has made it increasingly difficult and challeng- ing to make appropriate decisions about how to interpret tests, how to choose between different tests, and how to determine when imaging is indicated. Additionally, health care payers, providers and patients increasingly require evi- dence that imaging is useful, cost efficient, and beneficial. Outcomes research will guide these decisions, and if radi- ologists want to influence how and when these new tech- nologies are used, they must become active participants in understanding how such tests impact patients. Through outcomes research, the RORL will shape and advance the use of radiology by informing clinicians on currently opti- mal practices and by developing research techniques and strategies that will truly enhance patient health and quality of life. At present, we have only scratched the surface of what outcomes research and evidence-based radiology can achieve. The Radiology Outcomes Research Laboratory, through the generous support of the Department of Radiol- ogy, can provide the space, tools, and guidance for medical students, residents, fellows, and faculty members interested in working with our group to evaluate outcomes related to diagnostic testing. Through outcomes research, the RORL will shape and advance the use of radiology by informing clinicians on currently optimal practices and by developing research techniques and strategies that will truly enhance patient health and quality of life. C l i n i c a l a n d R e s e a r c h N e w s
  17. 17. 15 Medical diagnoses commonly rely on assessment of both the functional status and the anatomical condition of the patient. In a clinical setting, in vivo measurement of or- gan physiology, tissue metabolism, tissue perfusion, and other biological functions can be performed with radionu- clide-tracer techniques such as positron emission tomogra- phy (PET) and single-photon emission computed tomogra- phy (SPECT). However, radionuclide imaging has relatively poor spatial resolution, often is photon starved, and can lack anatomical cues that are needed to localize or stage the dis- ease. In comparison, imaging methods such as computed tomography (CT) or magnetic resonance imaging (MRI) have excellent spatial resolution, are rich in anatomical de- tail, but have limited functional content. To facilitate the process of correlating structural and functional information, investigators at UCSF and elsewhere have developed a new class of diagnostic instrumentation that combines X-ray CT and radionuclide imaging with SPECT or PET. These “dual-modality” systems use separate detectors for X-ray and radionuclide imaging, with the de- tectors integrated on a common gantry to simplify patient handling, data acquisition, and co-registration of the CT and radionuclide image data. The CT and radionuclide data are acquired with the patient in the same position to facilitate image correlation between the CT and SPECT or PET data. This makes it possible to produce a “fused image” in which the radionuclide distribution can be displayed in color on a gray-scale CT image to co-register the anatomical and physi- ological features and thereby improve evaluation of disease, in comparison to SPECT or PET alone. In addition, dual-modality imaging provides another benefit: that of improving quantitative functional assessments obtained with SPECT or PET. Specifically, conventional radionuclide images can be compromised by soft-tissue attenuation and by other physical effects such as scattered radiation. In dual-modality imaging systems, the CT data can be used to generate a patient-specific map of attenuation coefficients to correct the radionuclide image for photon attenuation. In this way, dual-modality imaging can improve both anatomical localization and quantitative accuracy of radionuclide imaging, and therefore it is gaining acceptance and is being adopted worldwide for clinical use. Dual-Modality Imaging with SPECT/CT Authors: Bruce Hasegawa, PhD Randall A. Hawkins, MD, PhD Clinical Implementation The conceptual design of dual-modality imaging sys- tems is quite simple. A typical dual-modality imaging has a CT scanner (X-ray tube and detector) and a radionuclide detector (PET or SPECT) mounted on a single gantry with a common patient table for X-ray and radionuclide imag- ing. CT and radionuclide scans are acquired by translating the patient from one detector to the other while the patient remains on the patient table. This allows the CT and radio- nuclide images to be acquired with a consistent scanner ge- ometry and body habitus, and with minimal delay between the two acquisitions. After both sets of images are acquired and reconstructed, image registration software then is used to fuse the X-ray and radionuclide images in a way that Figure 1: A prototype CT/SPECT system was configured at the UCSF Physics Research Laboratory within the Department of Radiology. It combined a GE 600 XR/T SPECT system with a GE 9800 Quick CT scanner for correlated anatomical and functional imaging. 15
  18. 18. 16 C l i n i c a l a n d R e s e a r c h N e w s accounts for differences in scanner geometry and image for- mat (e.g., 128¥128 vs. 512¥512) between the two data sets. Over the past decade, prototype PET/CT and SPECT/ CT systems have been developed by academic researchers, most notably at the University of Pittsburgh and at UCSF. More recently, commercial dual-modality imaging system have become available from the major medical imaging com- panies, including GE Medical System, Siemens Medical Sys- tems and CTI Incorporated, and Philips/ADAC Medical Imaging Systems. Finally, dual-modality systems for imag- ing small animals are being developed in both academic and corporate settings. At UCSF, researchers in the Department of Radiology, and specifically at its Physics Research Laboratory, pioneered the development of dual-modality imaging systems that com- bine X-ray CT and SPECT. The concept of dual-modality imaging at UCSF was conceived by Christopher Cann, PhD, Robert Gould, ScD, and Bruce Hasegawa, PhD, faculty mem- bers in the Physics Section of the Radiology Department at UCSF, and by Eric Gingold, PhD, a graduate student in Bioengineering at UCSF. Over the past decade, research with dual-modality imaging at UCSF involved theoretical mod- eling (Soo Chin Liew, PhD), computer simulations (Susan M. Reilly, MS), and development of the first prototype scan- ner (Thomas Lang, PhD). Implementation of a second pro- totype scanner included development of image reconstruc- tion techniques (J. Keenan Brown, PhD), and of new appli- cation-specific integrated circuits and detector characteriza- tion experiments (Joseph Heanue, PhD). These develop- ments led to quantitative measurements of radionuclide up- take in a porcine model of myocardial perfusion (Kathrin Kalki, PhD) with the prototype scanner. The development of these prototype systems led to the implementation of the first human-scale dual-modality sys- tem for clinical research (Figure 1) at UCSF (Stephen Blankespoor, MS) in collaboration with GE Medical Systems. The system was configured by siting a scintillation camera (GE 600 XR/T) adjacent to a commercial CT scanner (GE 9800 Quick), allowing the patient to be scanned first in the CT scanner, then moved into the SPECT system by simple translation of a common patient table. The first studies with this newer system included quantitative radionuclide assess- ments of myocardial perfusion (Angela J. Da Silva, PhD), again in a porcine model, and followed by the development of techniques for assessing cancer (H. Roger Tang, PhD), and for di- agnosis of prostate cancer patients with CT/SPECT (Kenneth H. Wong, PhD). Additional experimental studies have included development of new detectors and detector elec- tronics (Koji Iwata, PhD, William Barber, PhD). Scientists at the UCSF Physics Research Laboratory now are develop- ing a compact dual-modality system for imaging small animals (Andrew H. Hwang, BS, Anne E. Sakdinawat, BS) for biological studies at academic and corporate research centers. Important clinical expertise and scientific insight have been provided by Randall Hawkins, MD, PhD; David Price, MD; Gary Caputo, MD; and Mohan Ramaswamy, MD of the UCSF Nuclear Medicine Program. This concise history underscores the important contributions of many Figure 2: A GE Millenium VH (“Hawkeye”) SPECT/CT system recently was installed in the Nuclear Medicine Program within the Department of Radiology at UCSF. This system combines SPECT, coincidence imaging of FDG, and low-resolution CT in a single integrated system, and now is used for clinical imaging at UCSF.
  19. 19. 17 talented individuals in the Department of Radiology who have been responsible for the growth and development of dual- modality imaging research at UCSF. Dual-Modality Imaging at UCSF GE Medical Systems (Milwaukee, WI) and Elgems Ltd (Haifa, Israel) have developed a dual-modality imaging sys- tem (“Millenium VH” or “Hawkeye”) that combines SPECT and CT, similar to the approach developed at UCSF. The system performs planar scintigraphy or SPECT, and also performs coincidence detection of annihilation photons for imaging 18 F-fluorodeoxyglucose (FDG) and other positron-emitting radionuclides, and incorporates a low-resolution CT scanner for ana- tomical localization and attenuation correction of the radionuclide data. The Hawkeye system now is in- stalled in the Nuclear Medicine Clinic at Moffitt Long Hospital (Figure 2). It is interfaced both into the Radiology PACS system and into the Nuclear Medicinelocalareanetwork.Thismakes it possible to view images from the Hawkeye directly on the GE Integra workstation next to the camera, or on an additional Integra workstation in the Nuclear Medicine view room, and also on PACS terminals and on the Nuclear Medicine Pegasys (Philips ADAC) workstations. The system is used for both clinical and research studies. It has been used for routine clinical procedures (Figure 3) such as bone, renal and cardiac studies as well as for selected FDG coincidence imaging procedures. Single slice CT images having a slice width of 10 mm can also be acquired with the unit, and it is expected that in the future most nuclear medicine clinical studies will benefit from this level of co-registered CT acquired with nuclear medicine im- age sets. Areas of particular relevance of CT to clinical interpretation of nuclear medicine images include bone and whole body imaging. Figure 3: GE Millenium VH (see Figure 2) produces images that allow correlation of functional information from SPECT or FDG with anatomical information from CT. Illustrated above are images from a patient with metastatic melanoma. There is a focus of increased FDG (18 F-fluorodeoxyglucose) uptake in pedicle of T4 consistent with metastatic focus. Normally, the Hawkeye system is used to image single photon emitting radiopharmaceuticals, but the unit installed at UCSF has a thick crystal and coincidence circuitry, making it possible to image FDG and other positron emitting compounds as shown here. Images shown are CT on left (“Anatomic”), FDG in next row (“Physiologic”), and fused (combined) CT and FDG images in the next row, with a scout CT image on the right. A three-dimensional FDG projection image (lower right) shows additional metastases in the right humerus and multiple metastases in the spleen. A very promising capability of the technology is the improved attenuation correction in cardiac imaging. Because of the improved signal quantification the unit produces through more accurate attenuation correction and image seg- mentation approaches, it will be of particular value in new research protocols such as new radioimmunotherapy ap- proaches being developed together with investigators in Medi- cal Oncology and Pediatric Oncology at UCSF. This promises to make in vivo dosimetry with nuclear medicine radiopharmaceuticals much more accurate than with more traditional methods.
  20. 20. 18 C l i n i c a l a n d R e s e a r c h N e w s The Dynamic Neuroimaging Laboratory (DNL), located on the Parnassus campus of UCSF, utilizes a wide range of imaging and computational methods, emphasizing the inte- gration of EEG, MEG and fMRI to study spatial and temporal aspects of human brain function in health and disease. Why Brain Dynamics? The human cortex is an extended system of highly in- terconnected neurons, which function and process informa- tion both spatially and temporally. Most conventional radio- logical imaging techniques, e.g., X-ray and MRI, emphasize the spatial, while EEG and MEG emphasize the temporal. There are many viewpoints from which temporal dy- namics are essential for understanding brain function: • Populations of neurons generate net extracellular fields which act as macroscopic state variables; • Cognitive processing may often be decomposed into a temporal sequence of computations; • Normal brain function appears to involve the transient emergence and dissolution of large-scale cooperative net- works of activity, defining a global dynamics supporting perception and cognition; • Abnormal fluctuations reflect many pathologies, e.g., epilepsy, stroke, autism. By imaging both spatial and temporal aspects of brain Imaging Brain Dynamics Authors: Thomas Ferree, PhD Corby Dale, PhD, MPH Tracy Luks, PhD activity, we can begin to understand the functioning of dis- tributed neural networks underlying perception and behav- ior. This requires not only making the proper measurements, but also developing mathematical theories of how these sig- nals are generated by neural populations. Multimodal Neuroimaging Among the variety of techniques available for measuring brain activity, each has its own unique combination of spatial and temporal resolution, as shown in Fig- ure 2. Most significantly, PET and fMRI measure hemodynamic activity, while single-unit recordings, ECoG, EEG/MEG, and neuronal current imaging (NCI) mea- sure electrophysiological activity. Among the electrical measures, only EEG/MEG and NCI are noninvasive. The relationship between EEG and MEG deserves some clarification. EEG has been widely used since the 1930’s. When MEG was introduced in the 1980’s, it was first argued that it should have higher spatial resolution, because EEG is more distorted by the poorly conducting skull. With the advent of realistic head models that account for the skull and other head tissues, it has since become appreciated that the spatial resolutions of EEG and MEG are similar. Figure 2. Relative spatial and temporal resolutions of some techniques comprising multimodal neuroimaging. Figure 1. Artist rendering of several facets of multimodal dynamic neuroimaging. Color mapping indicates fMRI activity; yellow traces indicate EEG time courses; green lines indicate functional network connections between cortical areas. Morgan Hough Greg Simpson, PhD
  21. 21. 19 EEG/MEG results from the transmembrane currents of neocortical pyramidal neurons, whose apical dendrites lie along the local normal to the cortical surface. Synchronous activity of relatively few nearby neurons generates the fa- miliar current dipoles. The volumes sampled by EEG and MEG are also similar, but the geometries of the electric and magnetic fields are very different. MEG is nearly blind to radial dipoles, for example, while EEG sees both radial and tangential. At the level of the detectors, therefore, EEG and MEG are complementary. Simultaneous EEG/MEG record- ing and analysis are now considered state-of-the-art, and provide higher spatial resolution and accuracy than either method independently. Because EEG/MEG have lower spatial resolu- tion than fMRI, intuition suggests that a combined approach should be ad- vantageous. But because EEG/MEG and fMRI mea- sure different physiology, and their exact relation- ship is still poorly under- stood, this is not a trivial undertaking. We could argue that a first priority should be to understand better this relationship, e.g., through detailed electrophysiological and vascular models, as this would support their com- bined use in researching more complicated neuroscience questions. Integrative Neuroscience Rapid technological advances, exponen- tial growth in scientific literature, and increased specialization have led to a data overload in biomedical sciences. Now more than ever, real progress in neuroscience depends upon a close relationship between theory and experiment. Figure 3 depicts DNL’s current approach to this multifaceted problem. Integrated measurement refers to simultaneous acquisi- tion whenever possible, since biological systems are highly variable and sequential experiments never have identical control conditions. Integrated analysis refers to the use of different data sets, collected simultaneously or sequentially, to find globally optimal solutions that appropriately weight all the information. Neuronal current imaging (NCI) and diffusion weighted imaging (DWI) are at the development stage, and preliminary results suggest great promise as additional tools for integrated research. Experimental programs are best motivated from sound theoretical frameworks, continually refined and streamlined to better support interpretability of data. These theories may arise from various viewpoints, corresponding roughly to sci- entific disciplines. In neuroscience, we seek to understand Figure 3. The Dynamic Neuroimaging Laboratory’s current research activities and integrated approach. Figure 4. Modern dense-array (128-channel) clinical EEG system. Application time is under 10 minutes. [Photograph and EEG data courtesy of Electrical Geodesics, Inc., Eugene, Ore.]
  22. 22. 20 brain function in terms of underlying neuronal constitu- ents and their synaptic interactions, but realize that a purely reductionist approach might not be the most profitable. Models and analyses are all computationally intensive, and computation itself is a metaphor for brain informa- tion processing. At the DNL, we study brain function in both health and disease. Our emphasis in cognitive neuroscience is on attention and working memory. A better understanding of these processes in healthy subjects can guide clinical stud- ies in aging, dementia, schizophrenia, and autism. Pathophysiology of Acute Stroke As an example of how brain dynamics can reflect patho- physiology, we describe a recent study aimed at detecting acute cerebral ischemia. Dense-array (128-channel) EEG data were collected from 10 subjects, presenting in the emer- gency room with signs of recent stroke. Historically, analysis of EEG on paper charts looked for abnormal patterns, such as oscillations of a particular frequency or epileptic spikes. Later the estimation of fre- quency content was automated with Fourier transform and wavelets. But the question remains: How best to character- ize EEG time series? This question is of theoretical interest, because it queries the nature of the EEG signal, and there- fore the dynamics of large neural populations. It is also of practical interest, because the huge data sets produced by dense sensor arrays are too labor-intensive to analyze by eye. Furthermore, the eye may miss patterns in the data, which suitable algorithms might readily detect. The brain is obviously a complex system and, like most complex systems, it exhibits a very broadbanded power spec- trum, i.e., Fourier analysis reveals all frequencies contribut- ing significantly. While it is tempting to look for dominant peaks and interpret them as resonances of an approximately linear system, such an approach is not necessarily suitable for complex nonlinear data. An alternative approach is to quantify fluctuations across a range of time scales, and look for patterns in the data that are independent of scale. This is akin to the familiar fractal analysis, but applied to a time series rather than a static geometric object. In a study of 10 stroke patients and 18 normal control subjects, we found that with few exceptions 10-second seg- ments of resting EEG may reasonably be described with just two dimensionless parameters, called scaling exponents [Hwa and Ferree (2002), Physical Review E 66: 021901]. In Figure 5. The number of subjects with stroke score S. Open bars are 17 normal control subjects; filled bars are 9 acute stroke patients; scaled bar shows overlap of one subject from each group. addition to theoretical underpinnings suggesting that scal- ing exponents might be natural for describing the EEG, this parameterization has practical advantages for comparing across data channels and across subject groups. Using this method, the resting EEG for each of 28 sub- jects was reduced to 128 pairs of scaling exponents. It seems intuitive that a brain lesion like a stroke might change the distributions of the scaling exponents over the scalp. By considering the mean, variance, and higher moments for each subject, we were able to derive a direct physiological measure of brain function, called S, which linearly sepa- rates the two subject groups (Figure 5). This is a novel and remarkable step in data reduction, anticipated only by the general observation that many complex systems exhibit scale-independent behavior of some sort. We have half-jokingly likened our stroke measure S to the body temperature T, because it serves a similar clinical purpose. In both cases, many poorly understood physiologi- cal processes contribute to the measure, yet knowing just this one number can inform a physician about the likeli- hood of pathology. C l i n i c a l a n d R e s e a r c h N e w s
  23. 23. 21 Evolving Applications on the Interventional X/MR System Authors: David Saloner, PhD William P. Dillon, MD Chris Dowd, MD Roy L. Gordon, MD Van Halbach, MD Randall Higashida, MD Alastair Martin, PhD Maythem Saeed, PhD Kendrick Shunk, MD Oliver Weber, PhD Mark Wilson, MD Charles B. Higgins, MD Investigators are pursuing a broad range of studies using the unique capabilities of the Interventional X/MR system in the Department of Radiology at UCSF. In rou- tine clinical use, these two systems function independently as a state-of-the-art MRI system (Philips Medical Systems, Intera 1.5T MRI) and an X-ray angiography suite (Philips Medical Systems, Integris V5000 angiography system) in adjoining rooms. In research mode, the doors separating these two systems are opened and the patient table can be positioned either in the MRI scanner or in the angiography suite. Patients can thus be safely and quickly moved between the two modalities, providing the capability to monitor the effects of endovascular interventions on the surrounding soft tissue and on the end organ. The combined X/MR system has the potential not only to provide important information about the underlying physiological mechanisms that follow interventional treat- ments, but also to make it possible to reduce the technical challenges of many of these interventions. The placement of devices in specific locations can often be challenging, given the absence of clear information about the surrounding soft tissue and the difficulty of navigating through three-dimen- sional space using projection images alone. The possible benefit of using the combined X/MR system in the repair of atrial septal defects, for example, is currently under investi- gation in an animal model where X-ray guidance is used to advance a catheter to the site of interest. MR guidance is then used to deploy a device that occludes the hole in the septum. The three-dimensional capabilities of MRI aids in monitoring the intervention to ensure that one half of the device is deployed on either side of the septum, providing satisfactory occlusion of the hole. While focused on endovascular applications, re- search on the Interventional X/MR system is directed at dif- ferent organ systems, including neuro, body, and cardiac. Examples of three ongoing studies are presented below. Balloon Test Occlusion of the Carotid Artery Patients with intracranial aneurysms are at substantial risk of devastating injury if the aneurysm bleeds. In many instances aneurysms can be treated by packing the aneurys- mal space with balloons or coils, thereby excluding the an- eurysm from the parent vessel from which it originates. However, in other cases, such as unfavorable aneurysm ge- ometry, that procedure is not effective. If the territory supplied by the parent vessel has col- lateral supply, an alternative is to occlude the parent artery. This is the situation when the aneurysm arises from an internal carotid ar- tery where the contralateral carotid artery and the vertebral arteries can serve as sources of collateral flow. Before sacrificing the parent artery, it is necessary to determine whether the patient has sufficient collateral circulation to tolerate arterial sacrifice or whether a sur- gical bypass (such as an EC/IC procedure which shunts flow from the external to the internal carotid artery) must be performed. To test this, a temporary occlusion of the carotid artery is achieved by endovascular inflation of a balloon in the affected artery. Typically, these patients are monitored for neurological performance over a 30 to 60-minute exami- nation period to determine their tolerance for loss of this vessel. Neurological evaluations are relatively qualitative and it would be valuable to have aFigure 1
  24. 24. 22 C l i n i c a l a n d R e s e a r c h N e w s quantitative measure of the extent to which occlusion of a specific artery impacts on neurological function. MR may be a valuable tool for detecting subclinical ischemia during temporary occlusion of the carotid artery. We have been per- forming baseline perfusion, diffusion, post-contrast turbo- FLAIR, and flow measurements prior to occlusion and then repeating these measures during balloon inflation (Figure 2). Conventional diffusion weighted scans (b=1000 s/mm2 ) have not demonstrated perceptible changes during inflation, an effect that was unlikely considering the short time scales associated with test occlusions. Post-contrast turbo-FLAIR acquisitions, however, have demonstrated pial enhancement in brain parenchyma distal to the occluded carotid artery in some instances. First pass perfusion imaging further allows quantification of perfusion delays associated with collateral perfusion as well as elucidating hemispherical differences in blood volume and flow levels. The combination of these acquisitions may eventually provide additional parameters from which an improved determination of tolerance to ca- rotid occlusion may be assessed. Renal Artery Embolization Renal artery embolization is often employed in the treat- ment of tumors of the kidney. While catheter angiography provides an effective means of delivering the embolic agents, MR imaging has potential advantages in identifying the ex- tent to which the agent localizes in specific regions in the kidney (Figure 3). To evaluate this concept, we are investi- gating the use of microspheres that have been impregnated with Gadolinium, which provides a clearly identifiable sig- nal on MR images. The size of the microspheres can be se- lected to match the caliber of the intra-renal arteries and thereby control the depth of penetration at which embo- lization occurs in the renal parenchyma. We have found that the correlation of microsphere distribution with microsphere size is better appreciated on MR imaging than on catheter angiography. MR also provides a means to determine the rate of deposition of the microspheres on a region-specific basis throughout the three-dimensional geometry of the kid- ney. We are also investigating whether the use of the high- speed acquisition mode of the MR scanner, which can pro- vide real-time image acquisition at a rate of up to 10 fps, is an effective method for monitoring de- livery of the microspheres. In this mode, MRI clearly demonstrates the flow of the agent in the renal arteries and is a sensitive means of detect- ing reflux from the renal artery. Coronary Stenting The coronary arteries represent a substan- tial challenge for MR due to their small caliber and the degree to which they move during car- diac and respiratory motion. Accordingly, stenting of the coronaries demands a combination of high spatial and temporal resolution that only recently has become achievable. The use of MR to guide coronary stenting has some substantial benefits that will only be enhanced with the continued development of drug eluting stent designs. Nota- bly, MR may be able to depict regions of signifi- cant atherosclerosis independent of whether or not the plaque has created substantial narrowing of the lumen. Such information may provide a more appropriate target for placement of stents that attempt not only to improve vessel patency, but also to administer localized drug therapy. Coronary stent placement has been performed in an animal model (Figure 4). MR fluoroscopy Figure 2
  25. 25. 23 was achieved using an interactive viewer with a true tempo- ral resolution of 5 fps and a reconstruction rate of 10 fps. Three scan plane geometries corresponding to the aortic arch, the plane of the aortic valve and the circumflex artery were stored and used to subsequently monitor the procedure. It was possible to guide a catheter to the plane of the aortic valve and position it at the ostium of the left coronary ar- tery (frame B). Positioning was confirmed by puffs of dilute Gd solutions, whose path was visualized on T1 -weighted real- time acquisitions. A guidewire was then introduced in the circumflex artery and visualized via its stainless steel tip, which produced a relatively strong artifact (frames C, D). The nitinol body of this guidewire could not be visualized in this case so the passage of the tip was visualized in orthogonal planes along the coronary artery to assure its position prior to stent deployment. This study affirmed the possibility of using real-time MR scanning to deliver stents even to the most difficult anatomical locations, but reinforced the need for substantial improvements in opti- mizing the MR visibility of endovascular devices. Discussion The combined X/MR suite provides an interesting new opportunity to probe physiological responses following interventional procedures. In particular, physiological mea- sures such as volume flow and tissue perfusion as well as changes in the soft tissue signal can now be evaluated in the interval immediately following intervention. The com- bined system provides the potential to use MR to establish quantitative measures for determining whether a treatment has achieved its goal or whether additional interventions are needed. The capabilities of X/MR will expand as investigators develop devices that are better suited to the requirements of the different imaging environments. Indeed, a number of de- vices are being evaluated where the catheters and stents used in the treatment procedure perform double service in that they are also used as probes to boost the detected signal. The X/MR facility provides new and exciting challenges to radiologists and basic scientists in the Radiology Depart- ment. It fosters increased research collaboration with col- leagues in a number of other clinical services, and offers hope for effective new endovascular approaches to a variety of disease processes. Figure 3 Figure 4
  26. 26. 24 On September 11, a day that many spent in prayer and meditation, 75 people came to hear Robert Lull, MD, speak on “Is Nuclear Terrorism Possible?” After observ- ing a minute of silence for last year’s terror victims, Lull said, “I don’t want people to lose sleep over this, but in- formation is preferable to ignorance.” Lull, clinical professor of Radiology and chief of Nuclear Medicine at SF General Hospital, gave the lunch crowd an overview of basic radiation facts, emer- gency response principles and likely scenarios. As cur- rent president of the San Francisco Medical Society, he as- sured the audience that the City and County of San Fran- cisco has an emergency response plan that is among the best in the country. Lull also brought a different level of insight, having served in the military and as medical consultant at Inter-service Nuclear Weapons School at Kirtland Air Force Base in Albuquerque, N.M. Attempts to smuggle nuclear weapons and materials have occurred, Lull said, citing incidents in Munich and Prague. More frighteningly, the now deceased General Alex Lebed said in a 2000 “60 Minutes” interview that Russia “can’t account for or locate approximately 135 ‘suitcase size’ 1 KT fission nuclear weapons of the munitions type.” These misplaced weapons fueled Lull’s imagination. If one of the missing 1KT suitcases was exploded at the Transamerica building, he said, the devastation would stretch in a one-mile diameter circle around downtown, with lethal radiation exposure extending even farther. At the edge of the circle, winds would be 150 miles per hour, not to men- tion the thermal effects from such an explosion. “There would be more burn victims than all the burn beds in Cali- fornia,” he said. In addition to stolen weapons, experts fear terrorists will build “dirty bombs” by putting regular explosives, such as TNT, together with radioactive materials and then en- casing it in lead so it can pass undetected. Lull believes that using a dirty bomb has a couple of strikes against it: obtaining highly radioactive materials is actually difficult, the loss of life would be similar to a conventional weapon, and the rad levels released would not be that high. How- ever, a dirty bomb explosion could have devastating eco- nomic and social consequences in an urban area. Politically, it would be difficult to agree on when decontamination would be sufficient and “safe” enough. If there was such an attack, Lull said the first goal should be to treat life-threatening injuries and to remove patients from the high radiation zone. “I encourage people to do simple first aid things,” he said. “People don’t get a le- thal dose doing first aid—just don’t linger.” Radiation in the air has the advantage of being easily moni- tored, so that rescue personnel can deter- mine how long to be in an area or when to enter. Determining radiation exposure levels in individual victims is difficult. Once patients are stabilized, the best way to measure radiation dose is a simple lymphocyte blood test. “The lower the absolute lymphocyte count after 48 hours indicates the higher whole body radiation exposure,” he said. Lull reviewed four basic factors that will determine someone’s exposure: time, distance, shielding, and quantity. “Staying indoors makes a big difference in the amount of radiation exposure,” he said, noting that in the Chernobyl incident, people indoors received 3 rads compared to 10-15 rads for those unsheltered. He also recommended simple washing with soap and water, without abrading the skin, as an excellent way to reduce radiation dose from fallout or radioactive material in a dirty bomb. Although many people are stockpiling iodide tablets to avoid thyroid cancer, Lull is more realistic about the like- lihood of needing the pills. To be effective, they need to be taken within hours of an incident and are only useful if ra- dioactive iodine is released. That’s true in a nuclear power plant accident or nuclear bomb detonation but not likely for dirty bombs. Also, children are most at risk. “We should be making pediatric size iodide tablets,” he said. Lull reassured the crowd that an exposure of 100 rads or less is survivable. “Survival is possible between 300-800 rads although bone marrow failure is likely,” he said. He noted that in the Three Mile Island accident, nobody re- ceived more than 100 rads. “Three Mile Island was a signifi- cant event in our country,” he said, “but in terms of radia- tion release and risk, it was very, very small.” Nuclear Terrorism: What You Should Know If a 1KT suitcase was exploded at the Transamerica building, Lull said, the devastation would stretch in a one-mile diameter circle around downtown…“There would be more burn victims than all the burn beds in California.” 24 C l i n i c a l a n d R e s e a r c h N e w s
  27. 27. 2525 Effects estimated for a 1 kiloton nuclear weapon in San Francisco with detonation at the Transamerica building as hypothetical ground zero (red spot). At the edge of the approximately one-mile diameter circle (in blue) individuals would have a 50% chance of survival from the blast and thermal effects. The survival would be less than 50% for acute radiation effects at the edge of the circle. Individuals at the edge of the circle would experience the following: static overpressure would rupture eardrums, wind with debris would be 150 mph, clothing and newspapers would spontaneously ignite from thermal energy. Individuals closer to the hypocenter would experience significantly greater effects from blast, thermal, and acute radiation energy. Delayed high levels of radiation from fallout would be distributed according to wind and weather conditions. Despite the best preparation by medical teams, it’s im- portant to look at what happened at Hiroshima and Nagasaki. Lull observed that, of the 45 hospitals in Hiroshima, only three remained standing after the attack. He also noted that the number of doctors who could aid in the medical crisis that followed was reduced from 298 to 59. The words ‘radiation’ and ‘nuclear’ still invoke fear. Lull believes more education is necessary, and not just for the general public. “Physicians and even radiologists are not that knowledgeable about treating radiation exposure and con- tamination,” he said. “We don’t routinely deal with lethal radiation levels and contamination.” Lull’s parting advice? “If you see that big bright flash, duck for cover and stay indoors.” —Jennifer Gennari Shepherd
  28. 28. 26 Over the last three years, there has been a dramatic expansion in the number of students in the joint UCSF/UCB Bioengineering Graduate Group. This has been extremely valuable for the faculty in the Department of Radiology, as it has provided a welcome source of new students who are interested in finding laboratories to perform their thesis re- search and an increase in the demand for courses in bio- medical imaging. The large number of students and the need for expanded curriculum has required a substantial growth in the infrastructure for bioengineering research and educa- tion. The School of Medicine has recognized this need and taken the first steps towards forming a Department of Bioengineering at UCSF. A permanent home for the depart- ment and laboratory space for recruitment of new faculty has been identified in the Institute for Quantitative Biomedi- cal Research at the Mission Bay campus. This is expected to be available for occupation in the summer of 2004. To act as a focus during the transition to departmental status, a Division of Bioengineering has been formed in the School of Medicine, with an assignment of temporary space and start-up funds. The Chair of the Division is Sarah Nelson, PhD, who is responsible for directing the development of the Bioengineering program and, as a Professor of Radiol- ogy, for making sure that the interaction between the two disciplines progresses in a manner that is mutually benefi- cial. She is assisted by a committee of senior faculty from the School of Medicine who are active in bioengineering research and education. Since the Department of Radiology Development of Bioengineering at UCSF Author: Sarah J. Nelson, PhD contains the largest population of faculty in the joint UCSF/ UCB Bioengineering Graduate Group, including Sharmila Majumdar, PhD, co-chair of the group, it is serving as the administrative home for the Division of Bioengineering and has made a major contribution to improving the infrastruc- ture for students and faculty. The research areas that have been identified as being of interest for Bioengineering at UCSF are Cellular and Molecular Engineering, Complex Neural and Biological Sys- tems, Mechanobiology and Biomaterials, Biological and Medical Imaging, and Diagnostic and Therapeutic Engineer- ing. Recruitment of new faculty is expected to start in the fall of 2002 and will focus on attracting junior faculty from other institutions who can bring in new expertise and form a sound basis for building the educational curriculum. The number of faculty with primary appointments in Bioengi- neering is expected to grow to eight by 2008, with 15 to 20 faculty having secondary appointments. The operation of the joint UCSF/UCB Graduate Group will continue as laid down in its by-laws under the management of the Execu- tive Committee but will be able to offer a much broader curriculum to its students. In addition to the numerous existing laboratories at UCSF that are actively engaged in Bioengineering research, the new space in the Institute for Quantitative Biomedical Research will include resources that are of particular inter- est to faculty in Radiology. The first of these is a High Field MR Center that will include 3T and 7T whole body scan- ners. This will focus on the development of advanced tech- niques for high resolution MR imaging and multi-nuclear spectroscopy. It will complement the more application-ori- ented research that will be performed at the new Molecular and Functional Imaging Center that the Department of Ra- diology is planning to open in early 2003 in rented space close to the Mission Bay Campus. A second resource of interest in the Institute is the Bio- logical Imaging Center that will focus on new techniques for optical and electron microscopy of molecules, sub-cellular and cellular components. Other facilities such as chemistry laboratories for synthesizing molecular imaging probes, biosensors and therapeutic agents and computer laboratories for bioinformatics, algorithm development and modeling com- plex systems will be available for collaborative research. The proximity and overlap in faculty and students be- tween the Departments of Radiology and Bioengineering will strengthen their interactions and ensure that the two disci- plines continue to flourish at UCSF. Seated, Sharmila Majumdar, PhD (left) and Sarah J. Nelson, PhD, of the Division of Bioengineering, with administrative staff Sarahjane Taylor (left) and Hillie Cousart. C l i n i c a l a n d R e s e a r c h N e w s
  29. 29. 27 The Clinical PACS group had an eventful year. The good news is that the new version of software for our commercial PACS was installed with minimal disruption and has been working well. Unfortunately, we were saddened by the news that David Avrin, a co-director of the group, decided to leave UCSF and unite his family in Utah. David’s contributions as a leader and a friend cannot be replaced. We both miss him and wish him well. While our case volume continues to expand as does our data volume, the PACS has managed well. The upgrade to our Agfa system, which included both software and a change in the display platforms from Sun Unix to PC NT, was critical to our successful handling of the data volume and our ability to expand the number of displays. There are currently 54 thick client displays deployed both within radiology and in some high-image volume locations throughout the hospital. With the exception of mammography, all imaging within radiology is now digital. The last location using film, an outpatient Medical Office Building on Divisadero Street, now has a Fuji CR system. Some older modalities, such as our Siemens PET, which initially were difficult to connect to PACS, are now successfully connected. One digital mammographic unit, a GE Senographe, does connect to the PACS for image archive but its images are interpreted softcopy on a dedicated GE dis- play. Another challenging area is biplane neuroangiography; the equipment is connected to the PACS, but the need for film remains. This year, the Radiology Department received approval to purchase 100 PCs for the purpose of web access to im- ages. While interpretation within radiology is filmless, the demand for images outside the confines of radiology results in considerable film production. One limitation to web ac- cess has been the inadequate number of PCs throughout the enterprise, such as in patient exam rooms, where refer- ring physicians like to show images to patients. The Medi- cal Center’s Information Technology group is installing the new PCs in locations identified by Radiology. These PCs connect to the hospital backbone and allow secure image access from our web server. In addition, we added a CD burner system to the film library so that patients or others needing ‘films’ can instead get their images on CD, which comes with a viewer also burned onto the CD. The Clinical PACS group, in addition to the departure of David Avrin, has had other personnel changes. Howard Kwong is now our administrative assistant and Jonathan Seong has joined the group as a programmer analyst. They join the remaining members: David Luth; Gus DeGuzman; Albert Wong; Mark Day, who is responsible for software development; and Todd Bazzill, who is in charge of our net- works and system maintenance. The faculty is comprised of Drs. Kathy Andriole, Bob Gould and Ron Arenson. Also important to the group is our full-time Agfa service engi- neer, David Huber. Agfa, our commercial partner in PACS, also provides us with a part-time development engineer, Chip Augello, who is new this year. Clinical PACS Group Author: Robert G. Gould, ScD Standing (from left): Robert Gould, PhD, Albert Wong, Christopher Jovais, Mark Day, David Huber, Howard Kwong, David Luth, Wyatt Tellis, Chip Augello, Jon Seong. Seated (from left): Todd Bazzill, Katherine Andriole, PhD, Agustus C. De Guzman.
  30. 30. 28 Equipment Changes and Challenges Author: Robert G. Gould, ScD TheDepartmentofRadiologyhascompletedseveralprojects this year and started several more. Installations of two nuclear medicine gamma cameras, one in Long Hospital and one at Mt. Zion, were finished, as was the installation of two CT scanners. A GE “Hawkeye” gamma camera was installed within Nuclear Medicine in Long Hospital. This system is GE’s most advanced SPECT camera and combines a CT system with the dual crystal camera. Furthermore, our system has 1” thick crys- tals, 3/8” more than on GE’s standard camera, that improve sensitivity for high-energy imaging. The other gamma camera that was installed, a Philips/ ADAC “Forte” unit, is now in operation at Mt. Zion. This unit is connected to the miniPACS to which all the Philips/ADAC cameras located at Parnassus are connected and which in turn connects to the Department’s PACS for long-term image stor- age. At this time, all of Nuclear Medicine’s equipment, includ- ing the Siemens PET unit, is connected to the PACS. In Long Hospital, a new GE Ultra CT scanner has replaced the GE Lightspeed Plus scanner that was just installed last year. The displaced scanner was moved to Mt. Zion, replacing the old inpatient unit. The Ultra has the capability to acquire eight images simultaneously, while the Lightspeed Plus can acquire four. Both have an X-ray tube minimum rotation time of 0.5 seconds. The next CT change, which should occur before the end of the year, is to remove the first multi-slice machine that was installed at UCSF three years ago, a GE Lightspeed, and replace it with a 16-slice unit. This scanner is on order from GE and will be delivered as soon as we can get the room ready for the installation. In the ACC, we have increased our Digital Radiographic (DR) capabilities, switching out a radiographic room in the out- patientradiologyarea.ThissystemwaspurchasedfromGEwhen the ACC was remodeled two years ago, but because of our re- quirement that it have both a table DR detector and a wall stand, delivery was delayed until this year and came with a second DR detector for the wall stand. We have found DR to be very fast and capable of producing excellent images but, at least during the start-up phase, not always as robust as we had anticipated. We are also installing two DR rooms in the Moffitt radio- graphic area to replace all of the existing outdated radiographic equipment in this area. The equipment is being purchased from Philips and the construction plans are complete and on a desk in Sacramento. This project will be particularly challenging because we must continue to have some radiographic equip- ment operational during construction, which will occur in the middle of the Radiology Department. Thus, construction will be phased so that one room becomes operational before work begins on the other, which drags out the length of the project. The Breast Imaging Section, located in the Cancer Center at Mt. Zion, is now reading images from a mobile digital mam- mographic unit. This system is a GE full field digital mammo- graphic unit housed in a truck and, although owned by the Carol Franc Buck Breast Care Center, it connects to our PACS and images are read softcopy by our mammographers. Our plans for a PET/CT scanner to be installed at Mt. Zion near our Cancer Center are progressing well, but this project will probably not be completed until next year. One of the most exciting undertakings by the Department this year is still in the planning stage, but moving forward. The Department has workedsteadilytowards leasingapproximately 50,000 square feet off-campus, adjacent to the new UCSF Mis- sion Bay campus. This space would allow the expansion of several existing research programs as well as provide opportu- nities for new recruitments and new research possibilities. The centerpiece of this project is the development of a 3T research magnet program, the first in San Francisco. It would contain facilities to support existingandnewanimal researchand house a growing research computer function for the Department. We are also planning to install a cyclotron for production of both research and clinical PET isotopes at this location. In conjunction with the Department’s research space ex- pansion in this location, we are working with the UCSF Medical Centertoopenanewoutpatient-imagingcenteratthesamesite. Clinical imaging equipment for this site will include a 3T mag- net to be part of the research expansion, two 1.5T magnets with shell space for one more, and a CT scanner. We are planning for the addition of one CT scanner and one PET/CT scanner at this site in the near future as well. We believe that expansion of our clinical program in this location has tremendous potential and canbedevelopedquickly.Inaddition,itcontinuesaUCSFtradi- tion of locating clinical and scientific programs near each other to facilitate interactions between these groups. We hope to show you photographs of this new facility in operation in the 2003 Images! GE “Hawkeye” gamma camera which has been installed in Nuclear Medicine in Long Hospital. N e w F a c i l i t i e s a n d T e c h n o l o g y

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