Diffusion-weighted and Perfusion MR Imaging for Brain Tumor Characterization and Assessment of Treatment Response
1. Diffusion-weighted and Perfusion
MR Imaging for Brain Tumor
Characterization and Assessment of
Treatment Response- An Overveiw
3. Perfusion MR Imaging of Brain Tumors
: An Overview
Perfusion imaging of brain tumors has been performed by using various tracer and nontracer
modalities and can provide additional physiologic and hemodynamic information
Tumor vascular perfusion parameters obtained by using MR perfusion
1. tumor grading, prognosis, and treatment response I
2. differentiating treatment/radiation effects
3. non-neoplastic lesions from neoplasms
4. DW IMAGING & DTI
ADC: Apparent diffusion coefficient : represent microscopic water molecule diffusability in presence of
factors that restrict Diffusion
Eg:/ cell memberane, viscocity
In tumors with necrosis, surrounding oedema etc.
DTI , diffusion-tensor imaging provides a sensitive means to detect alterations in the integrity of white
Whitematter abnormalities can be seen on diffusion-tensor images that are not evident on routine MR
DTI tractography can provide guidelines fro surgical intervention and management.
Provide WM tract abnormalities very distal or far from Primary lesion.
5. Perfusion MR Imaging of Tumors
ANGIOGENESIS : In active (growing) lesions .
Lack of maturity. Increased permeability to macromolecules.
Fick principle;assumes a simple scheme in which the concentration of an agent is a function of the contrast
agent volume and the vascular volume.
This scheme does not adequately take into account the effect of extravasation of the agent.
Pharmacokinetic (multicompartment) model
scribes a more complex interaction between two compartments in the tumor:
the intravascular space and the extravascular extracellular space (EES)
6. Increased vessel tortuosity, immaturity, and permeability (seen in high-gradetumors) lead to an increase
in the permeability–surface area product.
. When a dysprosium based contrast agent is used, the rate of administration was found to affect the
shape of the time-enhancement curve
But not the area under the signal intensity–time curve, which is proportional to the relative cerebral
blood volume (rCBV)
Regions of high rCBV are thought to reflect areas of high capillary density,which is a reflection of tumor
7. Dynamic susceptibility-contrast (DSC) approaches are first-pass techniques that are T2- or T2*-weighted.
At high concentrations, the contrast agent induces substantial T2* shortening,
First in loss and then in recovery of signal in the tumor bed as the agent is redistributed or diluted.
DSC MR imaging can be performed by using either a gradient-echo or a spin-echo pulse sequences
GE-DSC is sensitive to larger vessels as in veins
SE-DSC is sensitive to smaller cappilaries; so more useful in assesement of the tumor
These methods can be safely used when the rate of vascular leakage is low.
When the rate of leakage is high, rCBV mapping results can be underestimated
Arterial spin labeling *is an endogenous contrast approach in which the patient’s own blood is magnetically
labeled with an MR prepulse prior to the blood’s entry into the imaging volume.
8. Perfusion parameters
rCBV: almost all studies have concentrated on rCBV assessment
A number of rCBV measurement methods exist,
1. placement of a single region of interest and calculation of the mean of repeated rCBV
but few studies have been performed on the reproducibility of rCBV measurements using this
2. Placing multiple regions of interest .
3. Permeability can also be assessed with the use of DSC images, which would allow one to obtain
both permeability and rCBV measurements from the same infusion of contrast.
The technique is not considered to be valid under conditions in which a very high degree of
contrastmaterial leakage is present, which is a limitation in many cases
9. Perfusion and DW MR Imaging for
, higher grade tumors would be expected to have higher rCBV
rCBV has typically been calculated by comparing the pathologic region to a corresponding
region in the contralateral hemisphere.
Most investigators have chosen to use a normal-appearing region in contralateral white matter
as a control region, which generally differs in location from patient to patient.
1. Values in high-grade tumor are typically seen to be at or near rCBV values in gray matter.
2. some evidence exists that nonglial neoplasms (eg, lymphoma) appear to have lower rCBV
than do high-grade glialneoplasms.
10. Relative cerebral blood flow and mean transit time, but they are less valuable in the evaluation
of brain tumors
high-grade tumors had heterogeneous rCBV maps with regions of high rCBV, whereas low-grade
lesions had only low rCBV.
12. MR Perfusion as guide for Stereotactic
More accurate preoperative grading of primary brain tumors could have a major effect on the
lives of patients with brain tumors, perhaps by leading to fewer biopsies.
Site to could be selected on basis of rCBV maps and areas with high rCBV values are biopsied.
1. Improves the chance of a positive accurate biopsy
2. Reduces no of biopsies
3. In Post operative recurrence suspected cases rCBV maps can provide information regarding
cellularity without a repeat Biopsy
14. Perfusion and DW MR Imaging for
Assessment of Tumor Therapy
rCBV is thought to correspond to microvessel density, early response to antiangiogenesis therapy
might manifest as a decrease in rCBV.
Alternatively, because some angiogenesis factors are permeability promoters, a decreased rate of
contrast material leakage might be an early indication of response to antiangiogenesis therapy.
monitor tumor angiogenesis and assess the response to antiangiogenic therapies.
A few initial studies have used dynamic contrast-enhanced MR to assess for tumor response to therapy.
An increase in ADC values compared to pre-therapeutic values confirms response(i.e reduced
Studies of patients with brain tumors have shown that increases in water diffusion generally indicate a
positive response to therapy
16. Radiation-induced Necrosis versus Tumor
The two entities can usually be distinguished by using positron emission tomography with
fluorine 18 fluorodeoxyglucose.
. Because recurrent high-grade tumor is characterized by angiogenesis (and typically high rCBV)
and tumor necrosis is generally less rCBV values.
Also can determine difference between normal brain and low-grade astrocytoma after radiation
DWI has no or Limited role in assessment of Post Radiotherapy changes.
One Study suggested when used in tandem with MRSpectroscopy it improves Positive Predictive
17. MR perfusion v/s CT perfusion
Perfusion CT and dynamic contrast-enhanced MR techniques were compared in
the same patient, a relatively good correlation was seen between the two
techniques with regard to the tumoral regions of highest permeability and
regions of highest rCBV.
18. DW MR Imaging for Definition of Tumor
In Morphologoic assessment of tumors usually unenhanced area adjacent to tumor is considered
the free margin of the tumor.
This model of tumor structure is oversimplistic for primary glial tumors, because tumor cells
areknown to extend into the unenhancing region of peritumoral edema and even into normal-
appearing white matter far from the primary lesion.
Tumors may have both enhancing and nonenhancing zones ; or even completely non enhancing.
A number of studies have shown that ADCs in peritumoral edema are higher for metastases than
for primary cerebral tumors
Some authors suggested that high-grade glioma could be differentiated from metastases and low-
grade glioma by using measurements in perilesional edema of a so called tumor infiltration index,
which is based on the relationship of fractional anisotropy to mean diffusivity
19. Several investigators have studied the application of DW and
diffusion-tensor imaging to delineation of the tumor margin. By and
large, the results of these studies do not correlate the location of DW
or diffusion-tensor imaging abnormalities with histopathologically
defined tumor boundaries; rather, the approach taken has been to
demonstrate differences in peritumoral characteristics in high- grade
liomas , which show some degree of tumor infiltration into non-
ehancing regions adjacent to the enhancing mass as compared with
low-grade gliomas, metastases, and meningiomas.
20. DW imaging with a high b-value (generally in the range of 3000–4000 sec/mm 2 ) allows the
characteristics of water diffusion to be studied in more detail.
With this technique, diffusing water molecules have been studied in different pools
Eg: slow diffusion , fast diffusing pools,
Help in differentiating tumor tissue from Peri-tumoral oedema.
In general a tumor cellularity has an inverse correlation with the ADC values
i.e more cellular : lower ADC values.
ADC measurements have been found to be decreased in lymphomas relative to measurements
in other intracranial tumors such as high-grade gliomas.
23. In Vivo Perfusion Imaging versus
Current standard for tumor grading is histopathologic as sessment of tissue.
inherent limitations : sampling error, interobserver variation, and a wide variety of
classification systems that are available*
Many are region variable especially large tumors with heterogenous enhancement.
Unless excision Biopsy done ; nothing can be confirmed especially regarding vascularity of the
Higher the grade more herterogenity in tumor less specificity in histo path alone
These limitations canfrequently result in inaccurate classification and grading of
gliomas due to sampling errors
24. Brain tumor angiogenesis is a continuously evolving process that can also be affected by various
in vivo perfusion imaging that can be repeated (unlike invasive procedures such as surgical
excision or biopsy)
Continued evolution of these tumors as well as treatment response.
25. MR PERFUSION v/s FDG-PET
A quantitative rCBV as calculated from a perfusion MRI scan might
be superior to the Lmax/Rmax ratio as derived from 18F-FDG and
11C-MET PET in order to distinguish a recurrence of high-grade
glioma from radiation necrosis.
Yong Hwy Kima, So Won Ohb, You Jung Limc, Chul-Kee Parka, e, , , Se-Hoon Leed, Keon Wook
Kangb, Hee-Won Junga, Kee Hyun Changc
Clinical Neurology and Neurosurgery
Volume 112, Issue 9, November 2010, Pages 758–765
26. Fourteen enhancing lesions could be classified as progressing (11) or
regressing (three). An empirical threshold of 2.0 ml/100 g for rCBV
allowed detection of regressing lesions with a sensitivity of 100 %
and specificity of 100 %. FDG-PET and DCE-MRI agreed in classification
of tumor status in 13 out of the 16 cases where an FDG-PET
classification was obtained. In two of the remaining three patients,
MRI follow-up and histology was available and both indicated that the
DCE-MRI answer was correct.
Vibeke A. Larsen, Helle J. Simonsen, Ian Law, Henrik B. W. Larsson, Adam E. Hansen
March 2013, Volume 55, Issue 3, pp 361-369
27. OTHER APPLICATIONS
ABSCESS V/S TUMOR
Perfusion MRI may allow the differentiation of pyogenic brain abscess from cystic brain tumors,
making it a strong additional imaging modality in the early diagnosis of these two entitie
In perfusion-weighted images, the capsular portions of the abscesses demonstrated low colored
areas compared with the normal white matter and the rCBV ratio calculated was 0.76 ± 0.12 (mean
The rCBV values in high-grade gliomas and metastases were 5.51 ± 2.08 and 4.58 ± 2.19,
respectively. The difference between abscesses and cystic tumors was statistically significant
Erdogan, Cuneyt MD*; Hakyemez, Bahattin MD*†; Yildirim, Nalan MD*; Parlak, Mufit MD*
September/October 2005 - Volume 29 - Issue 5 - pp 663-667
Neuroimaging: Original Article
Measurement of rCBV by using both dynamic contrast-enhanced (T1-weighted) and dynamic
susceptibility contrast (T2*-weighted) approaches have shown good correlation with World Health
Organization tumor gradES
A rCBV value of >2 suggests high cellular vascularity.
Diffusion-weighted (DW) imaging may allow the cellularity of tumors to be graded noninvasively*
A high ADC score suggest less cellularity and can be used to monitor Tumor Response to Therapy.
Overall tissue characterestics can be assessed more easily than Histopathology.
Studies of patients with brain tumors have shown that increases in water diffusion generally indicate
positive response to therapy.
Perfusion and DW MR imaging are providing insights into tumor behavior that are
not available from conventional MR imaging and Important for assessment of tumor
response to therapy than for diagnosis.
33. TAPV-R - SNowman
APVR can be classified into four types (in decreasing order of frequency) depending on the site of
anomalous venous union 1:
Type I: supracardiac
anomalous pulmonary veins terminate at the supracardiac levelpulmonary veins converge to form a left
vertical vein which then drains to either brachiocephalic vein, SVC or azygous vein
Type II: cardiac
pulmonary venous connection at the cardiac leveldrainage is into the coronary sinus and then the right
Type III: infracardiac
The pulmonary veins join behind the left atrium to form a common vertical descending vein
the common descending vein courses anterior to the oesophagus passes through the diaphragm at the
oesophageal hiatus and then usually joins the portal system
drainage is usually into the ductus venosus, hepatic veins, portal vein or IVC
Type IV: mixed pattern
35. Pellegrini-Stieda lesion
Pellegrini-Stieda (PS) lesions are ossified post-traumatic lesions at (or near)
the medial femoral collateral ligament adjacent to the margin of the medial femoral
condyle. One presumed mechanism of injury is a Stieda fracture (avulsion injury of the
medial collateral ligament at the medial femoral condyle). Calcification usually begins to
form a few weeks after the initial inju
Congenital cortical malformations characterised by absent or minimal sulcation.
type I (classic) lissencephaly
type II (cobblestone complex) lissencephaly
Type I (classic) lissencephaly can apear as the classic hour glass or figure-8 appearance or with a few
poorly formed gyri (pachygyria) and a smooth outer surface. It is usually associated with band
Type II lissencephaly on the other hand has a microlobulated surface referred to cobblestone
complex. There is not band heterotopia and the cortex is thinner than type I.
imaging is based on the principle that
molecules in any living tissue routinely
undergo random (brownian) motion
. The result is that
the neovessels often have both abnor-
mal flow characteristics and abnormal
permeability that can be exploited as
potential surrogate markers for the
evaluation of tumor growth.
bined T1- and T2-weighted ap-
proaches are sometimes used as well.
*. The authors of one relatively
recent publication (24) indicated that
this method compares favorably to ex-
ogenous contrast agent methods
The data from dynamic contrast-en-
hanced imaging can be analyzed by us-
ing the pharmacokinetic models
Dynamic contrast-enhanced MR imag-
ing approaches are based on T1 short-
ening produced by an infusion of para-
magnetic contrast material (17). T1-
based changes are primarily a result of
contrast material diffusion into the EES.
Dynamic imaging is typically performed
duringan interval of approximately 5–10
minutes rather than during the first pass
of the bolus.
It is im-
portant to note that one of the hall-
marks of high-grade lesions is tumor
heterogeneity; therefore, rCBV maps
often show only small foci of high rCBV.
ontrolled studies in which
samples from various regions in a tumor
are obtained might prove difficult to im-
plement but would be one means of es-
tablishing the preferred method of opti-
mization of the biopsy site.
Many stereotactic biopsies are now
performed with the aid of CT guidance.
Therefore, optimization of biopsy sites
by using perfusion CT would be an im-
Tumour response assessment
ADC value plotting
Increased ADC in Red
Decreased ADC in Green
The Chart x-axis ADC Y axis – number of pixels.
In some cases, re-
gions of radiation necrosis have shown
restricted diffusion on ADC maps,
which could potentially be confused
with infarction. The authors of one
study (116) that combined MR spec-
troscopy and DW imaging concluded
that although DW imaging data may
provide some information to help distin-
guish tumor from radiation necrosis, it
did not provide additional information
that was not already evident from MR
Similarly in thepediatric age group,water
diffusion has been found to be relatively
restricted in cellular brain tumors such
As medulloblastoma and other primitive
neuroectodermal tumors, compared with
diffusion measured in other lesions
the most common of
which is the WHO grading system
CBV measurements using DCE-MRI may predict the status of contrast enhancing lesions and give results very similar to FDG-PET with regards to differentiation between tumor recurrence and radiation necrosis.
*because cells constitute a relative
barrier to water diffusion, com-
pared with extracerebral space,
tumors that are more cellular
would be expected to show less
increase in ADC than tumors
that are less cellular
Tetralogy of Fallot
Boot shaped Heart
Chondrocalcinosi of Menisci
Cobble stoning of Transverse colon : Crohn’s Disease