Brain Imaging in Nuclear Medicine Presentation PDF

Lebanese university BRAIN IN NUCLEAR MEDICINE MOHAMAD HAIDAR M.D. Nuclear Medicine E-mail: [email protected]  Nuclear Neurology Functional Imaging – Limited anatomical information – Important details in processes of Blood flow : Brain death, Epilepsy…...

Lebanese university BRAIN IN NUCLEAR MEDICINE MOHAMAD HAIDAR M.D. Nuclear Medicine E-mail: [email protected]  Nuclear Neurology Functional Imaging – Limited anatomical information – Important details in processes of Blood flow : Brain death, Epilepsy… Receptor distribution Metabolic activity of tumors New Hybrid devices : SPECT/CT, PET/CT and PET MRI – Anatomy +Function at the same time. What is the difference? Radiology Nuclear Medicine Anatomical vs Functional Imaging „Bermuda Triangle“ of Imaging contrast MRIS PET-CT SPECT-CT PET NUC MRS Optical Imaging MRI CT US spatial resolution temporal resolution/ imaging speed On the left , a 1969 blood-brain barrier scan in cerebral lymphoma and on the right a PETMR study in frontotemporal dementia Different information What’s the diagnosis? Dead… Radiopharmaceuticals?  Principe of nuclear Medecine Injection (or inhalation or distribution/fixation acquisition ingestion)  Radiotracers = Radiopharmaceuticals radiotracer = molecule + radioactive isotope (vecteur) (marqueur) = + FDG FDG  Equipment Modern, versatile multi detector gamma cameras High and ultrahigh resolution collimators Pinhole collimator – True optical magnification and improved resolution – Essential for some studies e.g. thyroid scan in newborns – Useful for hip joint skeletal imaging and DMSA renal scans in young infants  PET and SPECT PET: Positron Emission Tomography and SPECT: Single Photon Emission Computed Tomography Use injected tracers Clinical as well as research applications: – Tumors – Epilepsy – Parkinson – Dementia  Equipment SPECT/CT – Oncological studies (MIBG, I‐131, sentinel node imaging) – Orthopedic indications PET/CT – Common indications Majority of pediatric oncology studies Fever of unknown origin Epileptogenic focus localization – High sensitivity, 3D PET Modern CT in hybrid cameras allowing dose reduction protocols Well counter for radioisotope GFR studies Clinical modalities PET / SPECT MRI  PET/CT and PET/MR Relative advantages and disadvantages of PET/CT and PET/MR M. Larobina et al.  PET/CT and PET/MR Quantitation and data analysis: SWOT matrix of PET/MRI with respect to PET/CT A. Ciarmiello, L. Mansi (eds.), PET-CT and PET-MRI in Neurology, Early PET and SPECT human brain studies Brain activation Hans F. Wehrl et al. J Nucl Med 2014 Nuclear STUDY  PET – Isotopes and Half Lives 15O 2 Minutes 13N 10 Minutes 11C 20 Minutes 18F 110 Minutes 68Ga 68 Minutes  Plan Brain tumors Dementia Epilepsy Brain death  Roles of PET in Brain Tumors Differentiation between malignant and benign lesion Grading brain tumors: High versus Low grade. Guidance for biopsy site Delineation of the extension of brain tumors Therapy monitoring Diagnosis of recurrence  Metabolic Tracers for PET Glucose metabolism – FDG PET: Grading, localization of malignant parts, tumor vs. necrosis Ion transport –Rb-82 PET Amino acids: Activated transport even in 70% of low-grade tumors; monitoring of therapy and progression; detection of recurrent tumor (vs. necrosis) – PET: C-11-methionine, F-18-fluoro-ethyltyrosine (FET), FDOPA, F-18-fluorotyrosine (F-TYR) Proliferation markers: C-11-thymidine, F-18-fluorothymidine (FLT) Intermediary metabolism: C-11 or F-18-labeled choline and acetate Hypoxia: F-18-fluoro-misonidazole (FMISO and related compounds Brain Tumor  MRI/PET MRI 18F-FDG PET High Grade Glioma  MRI/PET MRI 18F-FDG PET Low Grade Glioma  Limitations for using increased FDG uptake as indicator of malignancy High glucose metabolism in normal grey matter ▪ Dependent on neuronal function ▪ Further increase in focal epilepsy Glycolytic activity of macrophages ▪ Wide range of glucose metabolism in inflammatory lesions Tumor uptake not strictly related to malignancy – High uptake in some benign tumours: Schwannomas, rapidly growing meningiomas – Low uptake in some malignant lesions: Micronecrosis in GBM, metastasis.  Amino acid tracers Transport only Protein synthesis: F-18-fluoro-ethyltyrosine (FET) Transport and complex metabolism (Activity) – C-11-methionine – F-18-Fluoro-DOPA Transport and protein incorporation – C-11 tyrosine, – F-18-fluorotyrosine (F-TYR) Most tumors concentrate different amino acids more effectively than normal tissue  Aminoacids: 11C-Methionine Drawback: Short Halflife => Cyclotron onsite indispensable Transporter mediated Uptake No significant Metabolism in Proteinsynthesis Well established in Brain Tumours (positive Marker!) Most tumors concentrate different amino acids more effectively than normal tissue.  Aminoacids: 11C-Methionine Sensitivity up to 91% for Gliomas (n=23) Jacobs AH et al., JNM 12/2005 MRI 18F-FDG 11C-methionine Low Grade Astrocytoma  Aminoacids: 11C-Methionine Methionine superior to FDG in Follow up of treated Gliomas Sensitivity 89%, Accuracy 72% (11%, 36%, respectively) Methionine FDG Pötzi et al., J Neurooncol 2007 MRI 18F-FDG 11C-methionine  Aminoacids: 11C-Methionine Promising in Monitoring Chemotherapy Galldiks et al., EJNMMI 05/2006 Prognostic value of residual C-11- methionine uptake after resection Nariai et al., 2005  [11C/18F] tyrosine FET Mechanism of uptake : – largely incoporated in proteins – plasma metabolite; 50% at 1 hour after injection – transformed to DOPA (melanine synthesis) Application : brain, head and neck, lung, breast cancer Advantage : proteins synthesis rate Disadvantage : difficult to Produce  Aminoacids: 18F-FET Gliomas: FET + MRI => Sensitivity 93%, Specificity 94% (n=26) Variable Uptake in Low Grade Gliomas => No SUV-Cutoff 1/3 of Astrozytoma Grade II => No FET Uptake (similar to 11C- Methionine) Promising Tool in Detection of Recurrency Langen KJ et al., NMB 2006  Aminoacids: 18F-FET Gliomas: FET => Sensitivity 92%, Specificity 81%, Accuracy 92% (n=26) Significantly better than MRI alone in Assessment of Gliomas Pauleit D et al., Brain 2005 FET Amino Acid FET Amino acid  Aminoacids: 18F-FET High Value in Prediction of Prognosis of cerebral Gliomas Floeth FW et al., JNM 04/2007  In clinical practice, FET and MET have been shown to be equally sensitive and specific. In case of low-grade glioma FET can also reveal hot spots and suspected regions of histological upgrading of the tumor. In case of pseudoprogression, increase of the contrast enhancement on MRI is not associated with real tumor growth. In such situations, AA-PET as a functioning (Taal et al., 2008) imaging modality can help differentiate between real tumor progress and treatment related changes. (Popperl et al., 2007, Weber et al., 2000; Astner et al., 2005; Grosu et al., 2011).  Amino acid tracers for gliomas Strengths Limitations Increased uptake even in Not strictly tumor- most low-grade gliomas specific Clinically useful for (but still better than FDG) – Planning and Less informative for monitoring of therapy grading and prognosis – Location of most than FDG active tumor parts Often little uptake in – Study of infiltration metastases and lymphoma  Proliferation: 18F-FLT Halflife 110 Min. Nucleosid Analogue (Pyrimidin) Uptake by passive Diffusion / facilitated Transport Cellular Trapping after Phosphorylation by Thymidinkinase FLT  Proliferation: 18F-FLT Promising Results cerebral Gliomas: Suspected Recurrence Saga T et al., Clin Nucl Med 2006  [18F]FLT Brain MR FDG (SUV=0.3) FLT (SUV=3.5) [18F]FLT Brain: necrosis  Plan Brain tumors Dementia Epilepsy Brain death  Rationale for Imaging in Dementia Differentiation between various types of dementia to enable proper drug selection and evaluate prognosis Diagnosis before clinical manifestations of disease to allow drug therapy targeted at underlying pathologic condition and, potentially, a positive clinical response  Nuclear Study and Dementia Deficits in temporo-parietal metabolism seen in patients with AD Fronto-temporal dementias: decreased uptake in frontal and anterior temporal regions Depression: normal scan Vascular: patchy defects in central white matter Lewy body: deficits in occipital lobes and cerebellum  Comparing SPECT and PET SPECT has historically been a more widely available functional brain imaging for the evaluation of dementia. 89% sensitivity and 80% specificity for AD PET scans typically provide better spatial resolution, and the magnitude of hypo metabolism seen with FDG PET is generally greater than the amplitude of hypo perfusion seen with SPECT. Sensitivity 87-96%, 80% specificity Studies of AD using SPECT generally demonstrate less sensitivity and decreased overall accuracy  PET is approximately 15% to 20% more accurate than SPECT. tracer uptake reductions were significantly more pronounced with PET than with SPECT PET may be especially relevant when identifying disease in its earliest stages.  PET/MR imaging PET/MR imaging showing the progression of temporal atrophy and hypometabolism at different stages of cognitive impairment Brain Metabolism on FDG-PET Glucose Metabolic Patterns in Dementia Normal Alzheimer's Pick's: Frontal Dementia Lewy Bodies Multiple Infarct Huntington's Dementia PET scan can clarify the diagnosis, for example, can differentiate between AD and FTD, which is very important to guide the treatment. A negative PET may also reassure worried individuals that they have no evidence of a progressive neurodegenerative dementia (Mild cognitive impairment).  Mild cognitive impairment Alzheimer disease D.H.S. Silverman (ed.), PET in the Evaluation of Alzheimer’s Disease and Related Disorders, Cerebral Metabolism in Alzheimer’s Disease Progression and in Normal Brains Normal Early Alzheimer’s Late Alzheimer’s PET and SPECT in Central Motor Disorders Transaxial dopamine transporter (DAT) SPECT images  Plan Brain tumors Dementia Epilepsy Brain death  PET and SPECT are clinically indicated for pre-surgical localization of seizure origin. PET: – FDG-PET scan detects the regions of brain where the Glucose uptake is low (hypo-metabolism), which is often associated with the site of seizure origin. SPECT: – Brain Perfusion Study: measurement of blood flow to brain. – Radio-labeled chemical (ECD or HMPAO) is quickly injected at time of seizure onset to detect the region of increased blood flow, which is associated with seizure activity.  Inter Ictal Ictal Semin Nucl Med 42:371-386, 2012 Semin Nucl Med 42:371-386, 2012 Semin Nucl Med 42:371-386, 2012 Semin Nucl Med 42:371-386, 2012  Plan Brain tumors Dementia Epilepsy Brain death Negative radionuclide brain death scan In the flow phase, tracer is seen in the common carotids and anterior and middle cerebral arteries (double and single arrows, respectively). In the delayed phase, tracer accumulation is seen in the superior sagittal sinus (below image) and in the Cerebral Parenchyma(Left image). Positive radionuclide brain death scan In the flow phase, tracer is seen in the common carotid arteries (arrows), confirming an adequate bolus. No intracranial tracer activity is seen, including in the posterior fossa (curved arrow) in the delayed phase.  TAKE HOME MESSAGE Neuroimaging enhances sensitivity and specificity and helps in differential diagnosis in dementia. New technologies in neuroimaging will help to localize the epileptic focus. Metabolic imaging can be successfully used for the early detection of the effects of AD on the brain: regional brain damage may be limited. PET Brain for tumors can: Demonstrate metabolic heterogeneity within most Gliomas. Provide localized and specific information that is useful for ❑Targeting of biopsies ❑Early detection of recurrence.