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    Thorax cardio nsclc yw hang Thorax cardio nsclc yw hang Presentation Transcript

    • IMAGING OF NON SMALL CELL LUNG CARCINOMA NSCLC: 
 FROM MORPHOLOGY TO FUNCTIONAL IMAGING Dr. Yeung Wing Hang, Calvin Specialist in Radiology Hong Kong Baptist Hospital
    • MEDICAL IMAGING •  80s anatomical imaging: XR,CT,US •  90s anatomical imaging: CT,MR,US,DR •  00s functional imaging: DSCT, PET-CT, MR •  NEXT: ?
    • MEDICAL IMAGING •  80s anatomical imaging: XR,CT,US •  90s anatomical imaging: CT,MR,US,DR •  00s functional imaging: DSCT, PET-CT, MR •  NEXT: ?
    • MULTIDETECTOR CT (MDCT) 1971 1974 1989 1998 2001/2 RECENT First head CT scanner Body CT scanner Spiral/ helical CT scanner Multidetector CT (4 slices) Multidetector CT (16) 64,128,320,DSCT……
    • LN 4R 4L 10 7 10 11-14
    • LN 3A 4R 3P 4L 5
    • Mediastinal invasion T4
    • Vertebral invasion T4
    • Adrenal metastases M1b
    • Adenocarcinoma
    • Adenocarcinoma
    • NSCLC T2b (6cm)
    • Adenocarcinoma in situ
    • Adenocarcinoma in situ
    • Adenocarcinoma
    • Adenocarcinoma
    • Adenocarcinoma
    • Adenocarcinoma
    • MEDICAL IMAGING •  80s anatomical imaging: XR,CT,US •  90s anatomical imaging: CT,MR,US,DR •  00s functional imaging: DSCT, PET-CT, MR •  NEXT: ?
    • FUNCTIONAL IMAGING •  •  •  •  DUAL ENERGY CT IMAGING DIFFUSION WEIGHTED IMAGING PET-CT IMAGING PET-MR IMAGING
    • DUAL ENERGY CT 
 (DECT) IMAGING •  material differentiation, identification and quantification •  iodinated attenuation maps •  monochromatic images •  virtual unenhanced images
    • DUAL ENERGY CT 
 (DECT) IMAGING •  clear advantages in tumor detection, lesion characterization, and evaluation of response to therapy
    • DUAL ENERGY CT
 (DECT) IMAGING •  in the detection of oncology-related disorders (e.g., pulmonary embolism and bowel ischemia) and comorbidities (e.g., renal stones and gout)
    • DUAL ENERGY CT 
 (DECT) IMAGING •  application of two distinct energy settings •  to differentiate materials with different molecular compositions on the basis of their attenuation profiles •  result in a transition from attenuation based imaging to material-specific or spectral imaging
    • Dual Energy (Spectral) Imaging Can differentiate & classify tissue composition
    • DECT IMAGING IN NSCLC •   iodine maps for assessment of the relative vascularity of pulmonary nodules •  tissue enhancement can be accurately assessed on iodine maps
    • DECT IMAGING IN NSCLC •   on virtual unenhanced images, a reduction in the size of calcifications compared with that in actual unenhanced datasets •  there is a risk of overlooking small calcified lesions
    • DECT IMAGING IN NSCLC •  To the differentiation of calcification from enhancing tissue in solitary pulmonary nodules is made with a single contrastenhanced CT acquisition and virtual nonenhanced image reconstruction
    • DECT IMAGING IN NSCLC • DECT  could  serve  as  a  valuable  func3onal   imaging  test  for  pa3ents  with  NSCLC  as   iodine  related  a>enua3on  correlates  with   SUV  of  FDG  PET-­‐CT       (Schmid-­‐Bindert  G  et  al,  Eur  Radiol  2012)  
    • Adenocarcinoma
    • Adenocarcinoma
    • Adenocarcinoma
    • Non Small Cell Lung CA Water Image (VNC) Iodine Image
    • DECT EVALUATION OF RESPONSE TO THERAPY •   accurately assess the intratumoral amount of iodinated contrast medium to represent the perfusion and vascularization of lesion •  the iodine map is more robust parameter than attenuation (not influenced by intratumoral hemorrhage)
    • DISORDERS RELATED TO ONCOLOGIC THERAPY •   pulmonary thromboembolism •  bowel ischemia •  comorbidities in oncologic patients: renal stones and gout
    • Gout (Uric Acid Deposit)
    • Diffusion weighted image 
 of NSCLC •  DWI is sensitive to the random (Brownian) motion of water molecules. In biologic tissue, the presence of impeding barriers (e.g., cell membranes, fibers, and macromolecules) interferes with the free displacement (diffusion) of water •  The signal intensity in DWI depends on the separation and permeability of these impeding boundaries
    • Relationship between change in tissue cellularity and water mobility Free Diffusion: Increase in extracellular space and membrane permeability allow greater water mobility (eg water/ necrosis/ benign lesions) Result: High ADC value ADC: Apparent Diffusion Coefficient ) Restricted Diffusion: highly cellular environment, water diffusion is restricted because of reduced extracellular space and impermeability of cell membrane. (eg. Solid tumour/ malignancy) Result: Low ADC value
    • DIFFUSION WEIGHTED IMAGE (DWI) •  differentiation between benign and malignant tumour •  decreased Brownian motion of water in malignant tumour (increase cellularity) •  non-contrast, no ionizing radiation, fast
    • DIFFUSION WEIGHTED IMAGE (DWI) •  ADC has been correlated with important histologic properties, including the tumor proliferation index, tumor grade, the presence of necrosis, and tumor cell apoptosis •  ADC is highly reproducible
    • DIFFUSION WEIGHTED IMAGE (DWI) DWI ADC HIGH LOW Tumor, rarely abscess, viscous fluid, blood product HIGH HIGH T2 shine through, liquefactive necrosis LOW HIGH Fluid LOW LOW Fat, susceptibility arfefacts
    • DIFFUSION WEIGHTED IMAGE (DWI) False-positive findings: •  artifacts from image ghosting, poor fat suppression, or susceptibility effects. The clue to artifacts is that they may appear as recapitulation of structures seen elsewhere on the image or appear at boundaries between fat and water interfaces
    • DIFFUSION WEIGHTED IMAGE (DWI) •   normal lymph nodes •  tiny foci (typically 1–2 mm) of impeded diffusion are sometimes detected that are difficult to correlate with structures, ? small venules
    • DIFFUSION WEIGHTED IMAGE (DWI) False-negative findings: •  normal structures can exhibit impeded water diffusion, e.g. salivary glands, lymph nodes, spleen, spinal cord, ovaries, testes, red marrow, endometrial lining, bowel wall, peripheral nerves, and neural ganglia •  some of the well differentiated adenocarcinoma
    • Diffusion weighted image 
 of NSCLC •  Pathologic processes that alter the physical nature of the restricting barriers in biologic tissue affect the diffusivity of the water molecules, which can be visualized and quantified using DWI •  A known clinical application is diagnosis of acute ischaemic stroke
    • Diffusion weighted image 
 of NSCLC •  Important technologic advances, including echoplanar imaging, high-gradient amplitudes, multichannel coils, and parallel imaging, have extended the applications of DWI outside the brain •  Limitation of DWI in the thorax has been overcome by the demonstrated feasibility of DWI under free breathing (the concept of diffusion-weighted whole-body imaging with background body signal suppression)
    • Diffusion weighted image 
 of NSCLC •  Diffusion in biologic tissue is quantified by means of an apparent diffusion coefficient (ADC) •  At least 2 images with 2 different bvalues have to be acquired to calculate an ADC
    • Diffusion weighted image 
 of NSCLC •  Lesion–to–spinal cord ratio (LSR) was introduced, which is a semiquantitative measure that represents the ratio of lesion signal intensity to spinal cord signal intensity •  LSR takes into account both diffusion and T2 relaxation time, does not suffer from image misregistration
    • Diffusion weighted image 
 of NSCLC •  Kanauchi et al. : nodules with low signal intensity on DWI, comparable to or even lower than that of the spinal cord (i.e., LSR ≥ 1), were classified as positive on DWI. Otherwise, they were considered negative on DWI •  The SUVmax of DWI-positive patients (10.33 ± 4.93) was significantly higher (P < 0.001) than that of DWI-negative patients (3.10 ± 4.21)
    • Adenocarcinoma
    • WB Diffusion Stage IV Lung CA (lung, liver, LN, bone) NSCLC Pul. Mets. Liver & Spine Mets.
    • RadioGraphics November-December 2011 vol. 31 no. 72059-2091
    • 55/F NSCLC STAGE 4 21/10/2009   ADC:  1.01  x  103mm2/s   5/11/2009   ADC:  1.24  x  103mm2/s   23/11/2009   ADC:  2.15  x  103mm2/s  
    • DIFFUSION WEIGHTED IMAGE (DWI) •  Diffusion-weighted MR imaging might be useful for monitoring the early response to and the prognosis after chemotherapy of NSCLC •  Patients with advanced NSCLC might be able to avoid the cost of and cytotoxic damage from ineffective drugs and might be able to switch anticancer drugs early if drugs were deemed ineffective on the basis of early ADC change (Yabuuchi  et  al)    
    • 55/F Hx of CA lung, post lobectomy 3/6/2011 11/5/2012 3/6/2011 11/5/2012
    • Functional MR Imaging without Contrast MR Whole Body Diffusion Normal 40/M treated NPC with Lung Liver & Bone Mets 66/M Lymphoma
    • TUMOURS •    independence from growth signals •  insensitivity to growth-inhibitory signals •  evasion of apoptosis •  development of a limitless potential for replication •  development of sustained angiogenesis •  tissue invasion and metastasis
    • CT/PET Improve on the ability of the state of art CT to: •  detect tumour •  define the extent of tumour •  measure response to treatment
    • CT/PET •  FDG is not a target-specific PET tracer •  studies have shown that an SUV of 2.5 as the cutoff value will detect malignancy at sensitivity of 97% and specificity of 78%.
    • CT/PET •  a considerable reduction in SUV was associated with a pathologic response and proved to be a better predictor of long-term survival than anatomy-based criteria in patients with NSCLC who underwent neoadjuvant therapy, followed by complete resection
    • CT/PET •  a decrease in SUV >20% after one cycle of chemotherapy was associated with a longer time to progression and a longer median overall survival time in stage IIIB or IV NSCLC • significantly  longer  median  survival  3me  was   found  in  pa3ents  with  complete  metabolic   response  than  in  pa3ents  with  incomplete   metabolic  response  in  stage  IIIA-­‐N2  disease    
    • CT/PET •  a larger decrease in SUV was observed in responding patients than in nonresponders on CT imaging •  volumetric PET parameters could provide meaningful information about patient prognosis •  PERCIST (Positron Emission Tomography Response Criteria in Solid Tumors)
    • CT/PET •  FDG is not a target-specific PET tracer •  emerging new PET radiotracers may offer a clear opportunity to improve the study of many biologic features •  Fluoride-18-fluorothymidine (FLT) is used for the noninvasive measurement of tumor proliferation •  Cu(II)-diacetyl-bis(N4)-methylthiosemi- carbazone (Cu-ATSM) for hypoxia
    • CT/PET •  18F-FLT uptake is specific for malignant lesions and that there was a significant correlation between 18F-FLT uptake and proliferative activity •  18F-FLT PET imaging may have a potential role in the evaluation of response assessment in lung cancer, particularly when the treatment approach includes inhibitors of proliferative activity such as cyclin-dependent kinase inhibitors
    • MR/PET Advantages over PET/ CT: •  the superior soft tissue contrast of MRI allows better anatomical visualization of soft tissue structures and bone marrow than CT. •  simultaneous image acquisition enables temporal co-registration of dynamic PET data acquisition and morphologic/ functional MR data. MR perfusion, fMRI, DWI
    • MR/PET Advantages over PET/ CT: •  some studies comparing whole-body MR with PET/CT have shown potential advantages of MR particularly regarding the early detection of brain-, liver- and bone marrow metastases •  in fully integrated systems, MRI could also be used to provide a gating signal in addition to imaging
    • MR/PET •  PET/MR demonstrated higher sensitivity than PET/CT for all pulmonary nodules at 61.6 % and 70.3 % •  PET/MR delivered greater sensitivity than PET/CT in the detection of FDG-avid nodules at 94.4 % and 95.6 % •  sensitivity for small non-FDG-avid nodules was lower with PET/MR imaging than with PET/CT (Hersh Chandarana et al)
    • MR/PET •   Contraindications of MR scan, eg. most types of cardiac pacemakers and implanted defibrillators as well as certain metallic implants  
    • NEW DRUGS •  target the EGFR pathway in NSCLC, smallmolecule inhibitors of the tyrosine kinase domain of EGFR were developed (erlotinib and gefitinib) •  activating EGFR mutations were discovered in cancer cells from patients with NSCLC who responded to the targeted therapy with gefitinib and erlotinib
    • NEW DRUGS •  EGFR mutations in lung adenoCA are seen in approximately in 15% of patients in the United States and in 30% to 50% of patients in Asia •  clinical features are known to be associated with both EGFR mutations and response to gefitinib and erlotinib, including nonsmoker status, Asian ethnicity, and female gender
    • NEW DRUGS •     morphological assessment, RECIST uses unidimensional measurements of the sum of the longest lesion diameters •  many targeted agents are cytostatic and therefore tumor shrinkage may not be seen
    • NEW DRUGS •    functional imaging techniques, such as perfusion CT, dynamic susceptibility contrast MR imaging, dynamic contrastenhanced (DCE) MR imaging, or diffusion-weighted MR imaging, provide information on tissue phenotype or behavior
    • NEW DRUGS Comparison of Cytotoxic Therapy versus NODs •  Tumoral effect: Cytotoxic Vs cytostatic •  Criteria for tumor response: Tumor shrinkage Vs Tumor stabilization or shrinkage •  Imaging techniques for response evaluation: Anatomic (size and appearance) Vs functional or molecular imaging
    • NEW DRUGS Comparison of Cytotoxic Therapy versus NODs •  Time of response evaluation: Late (2 mo) Vs Early (2–6 wk) •  Toxic effects of drugs Usually nonspecific: multisystemic involvement Vs Less toxic: target-specific toxic effects  
    • RadioGraphics November-December 2011 vol. 31 no. 72059-2091
    • MEDICAL IMAGING •  80s anatomical imaging: XR,CT,US •  90s anatomical imaging: CT,MR,US,DR •  00s functional imaging: DSCT, PET-CT, MR •  NEXT: MOLECULAR IMAGING
    • MOLECLAR IMAGING • Molecular  imaging  is  expected  to  have  a  major   impact  on  the  early  diagnosis  of  diseases  and   disease  monitoring  in  the  next  decade   • Nuclear  imaging  techniques  have  been  the   mainstay  of  molecular  imaging  in  the  clinical   arena   • Con3nued  development  of  molecularly   targeted  contrast  agents  for  nonnuclear   imaging  techniques  such  as  MR,  CT  and  US
    • MOLECULAR IMAGING
    • CONCLUSION Along with molecular metabolic mechanisms of tumor cells that increasingly come to light, rapid development of functional and molecular imaging has taken place in recent years. By directly visualizing and measuring the biological process in vivo, functional and molecular imaging enables early assessment of response to anticancer treatment for NSCLC patient
    • THANK YOU