PET Imaging in Neurology

PET Neurology After completing this course you should be able to:   Identify areas of the brain anatomy   Communicate the concept of cerebral blood flow   Identify characteristics of a stroke and its implications on brain function   Recognize symptoms of dementia, Alzheimer’s and other memory disorders   Recognize symptoms of movement disorders and the causes behind them   Prepare a patient for PET Neuro imaging   Identify the radiopharmaceuticals used for brain imaging and how each is beneficial   Outermost Layer Gray Matter Contains: Nerve cell bodies Myelinated nerve fibers Functions Analysis of sensory data Performance of memory functions Learning new information Formation of thoughts Decision making Sequential Analysis Systematic Logical interpretation of information Production of symbolic information Language Mathematics Abstraction Reasoning Memory Stored in language format Responsible for holistic functioning Processes multiple sensory input simultaneously Get the "whole" picture of one's environment Processes visual and spatial stimuli Dancing and gymnastics Memory Stored as auditory, visual, and spatial modalities Cognition and Memory Concentration Attentiveness Thought elaboration Gatekeeper   Judgement Inhibition Personality Emotional traits Voluntary motor activity Storage of motor patterns and voluntary activities Motor speech Involuntary emotional expression disorder Lack of emotional reactivity Contra lateral plagia and paresis Expressive/motor aphasia Impairment of recent memory Inattentiveness Inability to concentrate Lack of inhibition Difficulty in learning new information Spatial Sense Navigation Body Orientation Tactile Sensory Inability to discriminate sensory stimuli Inability to recognize parts of the body Inability of self-recognition Inability to discriminate sensory stimuli Disorientation of environment and space   Inability to write Primary visual reception Primary visual association area Loss of vision in the opposite field Flashes of light or stars Auditory receptive and association area Processing semantics in both speech and vision Long term memory formation Hearing deficits Agitation Irritability Childish behavior Paleomammalian brain Set of brain structures Most primitive brain structure Hunger Thirst Response to pain Levels of pleasure Sexual satisfaction Aggressive behavior Controls wakefulness Increases flow of adrenaline Important emotional center Controls molecules for:    - Exhilaration    - Anger    - Unhappiness Negative emotions Anger Sadness Storage of unconscious traumatic memories Turns short term memories into long term memories Master Gland      - Controls functions of other endocrine glands Hormones Produced   - TSH - Prolactin   - ACTH - Growth hormone   - FSH - Oxytocin   - ADH - Melanocyte-stimulating hormone   - LH   Processing Center - Processes and relays sensory information selectively to various parts of the cerebral cortex - Regulates sleep and wakefulness Subcortical Gray Matter Processing link between the thalamus and the motor cortex Involved with coordination of voluntary motor movement - Balance - Equilibrium - Muscle tone Location is just above the brain stem at the back of the brain Impairment of the cerebellum - Tremors - Involuntary movements of the eye - Lack of coordination Where brain meets spinal cord Neuroloical functions for survival - Breathing - Heart rate - Blood pressure - Digestion - Arousal Relay station between spinal cord and brain Contains the following centers: - Respiratory - Vasomotor - Cardiac - Reflex Nerve pathway between cerebral hemispheres Contains auditory and visual reflex centers Controls: - Visual systems - Auditory systems - Eye movement - Body movement Superior to the medulla oblongata and inferior to the midbrain Contains important neuronal pathways arising from the cerebrum, spinal cord and cerebellum Relay station for messages Regulation of breathing Cerebral Blood Flow and Metabolic Imaging                                                                                         Image courtesy of St. Claraspital, Basel Switzerland Regional Brain Flow (rCBF) ● Continuously regulates the supply of oxygen and glucose ● Functional activation of the brain is followed by:   - Increased cerebral blood flow   - Increased glucose consumption   - Minimal increase in oxygen consumption Cerebral Metabolic Rate of Glucose (CMRglc) ● ml/min/100 g brain tissue ● Important diagnostic tool   - Oncology   - Other physiological processes Image courtesy of ABC News Symmetry ● Normal activity not completely symmetrical   - When viewing images, several adjacent slices should be viewed ● Conditions at the time of injection can induce asymmetry   - Eyes and ears open   - Increased glucose consumption Metabolic Flow ● Some brain regions have more prominent metabolic flow or activity   - Frontal eye fields   - Cingulated cortex   - Wernicke region   - Visual cortex   - Parietal lobe rCBF ● Controversial if declines with CMRglc ● Decrease in cortical metabolism with normal aging, especially in the frontal lobes rCBF ● Energy metabolism depends on the oxidation of glucose ● Brain is unable to store oxygen or glucose   CMRglc ● Low at birth ● Rapidly rise to adult values by age 2 ● Rate rises above adult values until age 9 ● Declines to adult rates in late teens Metabolism and blood flow activity is 4 times higher in gray matter than white matter.   Injection ● Movement or talking will increase activity in basal ganglia, motor cortex and language centers ● Eyes open:  Increased metabolic activity in visual cortex   Uptake ● Watching TV:  Increase glucose metabolism in the visual and auditory cortical areas ● Significant decrease in frontal areas Image courtesy of BehaviorAdvisor.com Overview of Dementia   Clinical Syndrome ● Impaired short and long term memory ● Deficits in: - Abstract thinking - Judgement - Other higher cortical ● Personality changes ● Develops mostly in the elderly ● 5-8% of people over 65 have some form ● By 80s, half will have dementia ● Diseases that cause degeneration or loss of nerve cells - Alzheimer's   - Parkinson's   - Huntington's ● Diseases that affect blood vessels   - Stroke ● Toxic reactions ● Nutritional deficiencies   - Vitamin B 12 and Folate ● Infections of the brain and spinal cord ● Certain types of hydrocephalus ● Head injury ● Kidney, liver, and lung diseases ● Long term substance abuse dementia ● Removable tumors ● Subdural hematomas ● Normal pressure hydrocephalus ● Metabolic disorders ● Hypothyroidism ● Hypoglycemia ● Alzheimer's ● Multi-infarct dementia ● Dementias due to Parkinson's and similar disorders ● AIDS dementia complex ● Creutzfeldt-Jakob disease Image courtesy of WVU ● Most common dementia disorder ● Affects ~4 million people in the US ● Onset typically over age 65 years ● Prevalence increases with age ● Younger people can be affected Intellectual Functions ● Memory ● Comprehension ● Deterioration of speech ● Attention ● Simple calculations ● Ordinary daily activities affected ● Agitation ● Frustration ● Bewilderment Early Onset ● Rare Late Onset ● Most common form ● 90% of cases ● Occurs after age 65     Earlier Onset ● Runs in families ● Onset in 40s ● Very rare, less than 1% of all cases Neurodegeneration of cerebral cortex   ●  Temporal lobes   ●  Parietal lobes   ●  Frontal cortex     ● Extracellular Beta-amyloid Plaques (Aß) ● Intracellular tau-associated neurofibrillary tangles (NFTs) ● Neuronal loss ● Neuroinflammation ● Synaptic Depletion Image courtesy of nlm.nih.gov Amyloid β Peptides ● Normally soluble and clear away ● Become insoluble ● Collect in intercellular space ● Corralled by chaperone proteins ● Large plaques form ● Damage neurons ● Attract reactive cells     ● Normally stabilize microtubules in brain cells ● Abnormal chemical changes cause:      ● Assemblage into spirals   ● Helical filaments   ● Create tangles   ● Disrupt cell functions   ● Leads to apoptosis Patterns of amyloid deposition in white and grey matter.   syngo®.PET Amyloid Plaque is intended for use only with approved beta-amyloid radiopharmaceuticals in the country of use. Users should review the drug labeling for approved uses. Precuneus ratio = 1.01 Parietal ratio = 1.04 Whole Brain SUVr = 0.94   syngo.PET Amyloid Plaque is intended for use only with approved amyloid radiopharmaceuticals in the country of use. Users should review the drug labeling for your country. ● Amyloid PET imaging study with Mild Cognitive Impairment (MCI) ● Increased uptake in precuneus, frontal, parietal and lateral temporal cortex syngo®.PET Amyloid Plaque is intended for use only with approved beta-amyloid radiopharmaceuticals in the country of use. Users should review the drug labeling for approved uses. Precuneus ratio = 2.00 Parietal ratio = 1.64 Whole Brain SUVr = 1.50   syngo.PET Amyloid Plaque is intended for use only with approved amyloid radiopharmaceuticals in the country of use. Users should review the drug labeling for approved uses. Other types of dementia include: Image courtesy of guardianlv.com ● Lewy Body Disease ● Frontotemporal Dementia ● Vascular Dementia ● Creutzfeldt-Jakob Disease ● Progressive brain disease ● Second leading cause of degenerative dementia in elderly ● 20% of all dementia causes ● Abnormal protein deposits found throughout the brain   ● Depletes brain of acetycloine     ● Disruption of:       ● Perception       ● Thinking       ● Behavior ● Umbrella term for uncommon disorders that primarily affect the frontal and temporal lobes of the brain ● Portions of the lobes shrink ● Dramatic changes in personality ● Inappropriate compulsive behavior ● Loss of ability to understand language ● Occurs between 40 and 70 years of age Image courtesy of the WVU   ● Most common form of dementia after Alzheimer's ● Group of syndromes relating to different vascular mechanisms ● Preventable ● Stroke victims are at increased risk of vascular dementia Image courtesy of the WVU   Prions ● Infectious agents composed of proteins ● Similar to bovine spongiform encephalopathy (Mad Cow Disease) Characteristics ● Rapid progressive dementia ● Insomnia ● Myoclonus (muscle twitches) ● Movement disorders ● Cerebral metabolic rate of glucose is severely reduced in multifocal fashion Image courtesy of A.D.A.M.com through nlm.nih.gov Movement disorders include: Image courtesy of Brighamandwomans.org ● Parkinsonian Syndromes ● Parkinson's Disease ● Idiopathic Parkinson's Disease Groups ● Idiopathic Parkinson's Disease (PD) ● Multiple System Atrophy (MSA) ● Secondary to other disorders or exogenous agents Image courtesy of the WVU Clinical Syndrome ● Tremor ● Rigidity ● Postural imbalance ● Bradykinesia Image courtesy of  the Royal Prince Hospital of Australia Degeneration of nuclei in dopamine cells in the brain stem Dopamine ● Neurotransmitter ● Stimulates motor neurons ● Depletion of dopamine ● Motor neurons unable to control movement and coordination ● 80% of motor neurons lost when symptoms appear Image courtesy of  Holy Name Medical Center, Teaneck NJ Most common form of Parkinson's Disease ● Marked left and right asymmetry ● Good symptomatic response to L-DOPA therapy ● Precursor to:   ● Dopamine   ● Norepinephrine   ● Epinephrine F18 - Fluorodeoxyglucose (FDG)     Most widely used isotope in PET imaging FDG PET/MR Brain Glioblastoma Image courtesy of Unitversity of Erlangen   ● Half-life of 109 minutes ● Labeled with glucose - Fluorodeoxyglucose (FDG) ● Taken up by high glucose using cells of the brain ● Phosphorylation   ● Prevents gludose from being released once absorbed Primarily used for: ● Brain metabolism ● Epilepsy ● Various brain tumors ● Currently FDA approved for use as a tool for diagnostic evaluation of AD   ● Binds to beta-amyloid brain plaques   ● Suitable for routine clinical use   ● Sort acquisition time (5-10 minutes) ● Investigational in the US ● Crosses the blood-brain barrier ● Taken up by dopamine receptors ● Regional distribution of dopamine ● Study presynaptic striatal dopaminergic function of PD ● Concentrates in the caudate, putamen and midbrain in normal patients. ● PD patients have diminished uptake in the opposite side of major motor dysfunction. NOTE: F18 FDOPA referenced herein is not currently  recognized by the US FDA as being safe and effective, and Siemens does not make any claims regarding its use. Image courtesy of the Journal of Nuclear Medicine ● Amino acid radiolabeled with fluorine ● Increase of amino acid transport to tumors ● Actively taken up by tumor cells ● Neither incorporated nor degraded ● High intracellular concentrations of this agent F18 FET PET/MR study of high grade glioma Image courtesy of JLVMI Consulting F18 Fluorothymidine (FLT) ● Investigational tracer ● Targets proliferating tissue and primary cancers ● Thymidine kinase activity proportional to cellular proliferation and DNA synthesis F18 FLT referenced herein is not currently recognized by the US FDA as being safe and effective, and Siemens does not make any claims regarding its use. Images courtesy of International Scientific Journals from Jaypee C11 Methionine (MET) ● Locate and differentiate primary brain tumors ● Monitoring Rx Therapy ● Naturally occurring amino acid ● Amino acid utilization processes   ● Transport     ● Protein synthesis     ● Transmethylation   ● Highest radioactivity concentration at 35 to 40 minutes post injection Image courtesy of Society of Nuclear Medicine and Molecular Imaging ● Normal fasting plasma glucose level of at least 6 hours ● Dose:  5-10 mCi ● Uptake:   ● Patient should be resting   ● Eyes closed   ● Ears unplugged   ● No physical activity   ● Time:  20-60 minutes ● Conditions that can affect global levels of FDG distribution   ● State of consciousness   ● Sensory influences   ● Anxiety   ● Sedative drugs Overall uptake is affected depending on sleep cycle ● Slow wave sleep:  Global decrease in CBF ● Anxiety during REM phase:  Increases CMRglc Avoid sleep during uptake periods Resting State ● No specific sensory stimulation ● No engagement in a behavioral or physical task ● Quiet uptake area needed ● Recommend eyes closed throughout procedure ● Make patients familiar with surroundings prior to exam to avoid anxiety and restlessness ● Not possible to control all patient's mental functions Global reduction in CMRglc and CBF ● Propofol ● Sevoflurane ● Isoflurane ● Halothane Increase in CMRglc and CBF ● Ketamine ● Related anesthetics Benzodiazepine Effects ● Most pronounced in the thalamus and occipital cortex Opioids (Morphine and Buprenorphine) ● Reduces CMRglc Influence CBF and CMRglc ● Some will increase in certain areas of the brain ● Acetazolamide ● Adenosine Static PET Acquisition ● 5-10 minutes in length ● 50-200 million detected events Dynamic Acquisition (if possible movement is suspected) ● Example:  Six 5 minute frames ● Add frames together that do not exhibit motion ● Dose:  5-20 mCi ● Uptake Period:  30 minutes ● Patient should be able to lie still for 30 minutes ● Immobilization devices are recommended ● CT scan should be acquired for AC Data courtesy of the European Journal of Nuclear Medicine ● Dose:  10 mCi ● Uptake Period:  30 - 50 minutes ● Patient should be positioned supine on scanner to include the cerebellum in the FOV ● Immobilize head using restraints ● CT with or without contrast should be acquired for AC ● PET Acquisition:  10 minutes Image courtesy of Siemens Medical Solutions Data courtesy of the Medscape.com Image courtesy of iop.org Fludeoxyglucose F18 injection (18F FDG) is indicated for positron emission tomography (PET) imaging in the following settings:   ● Oncology: For assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis of cancer.   ● Cardiology: For the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging.   ● Neurology: For the identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures. ● Radiation Risk: Radiation-emitting products, including Fludeoxyglucose F 18 Injection, may increase the risk for cancer, especially in pediatric patients. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker.   ● Blood Glucose Abnormalities: In the oncology and neurology setting, suboptimal imaging may occur in patients with inadequately regulated blood glucose levels. In these patients, consider medical therapy and laboratory testing to assure at least two days of normoglycemia prior to Fludeoxyglucose F 18 Injection administration.   ● Adverse Reactions: Hypersensitivity reactions with pruritus, edema and rash have been reported; have emergency resuscitation equipment and personnel immediately available. ● Multiple-dose 30 mL and 50 mL glass vial containing 0.74 to 7.40 GBq/mL (20 to 200 mCi/mL) of Fludeoxyglucose F 18 injection and 4.5 mg of sodium chloride with 0.1 to 0.5% w/w ethanol as a stabilizer (approximately 15 to 50 mL volume) for intravenous administration.   ● Fludeoxyglucose F 18 injection is manufactured by Siemens’ PETNET Solutions, 810 Innovation Drive, Knoxville, TN 39732.   This concludes the course PET Imaging in Neurology. You should now be able to: ● Identify areas of the brain anatomy ● Communicate the concept of cerebral blood flow ● Identify characteristics of a stroke and its implications on brain function ● Recognize symptoms of dementia, Alzheimer’s and other memory disorders ● Recognize symptoms of movement disorders and the causes behind them ● Prepare a patient for PET Neuro imaging ● Identify the radiopharmaceuticals used for brain imaging and how each is beneficial