Dr Hussein Farghaly PSMMC Radionuclide Brain Imaging Lecture 3 Master Watermark Image: http://williamcalvin.com/BrainForAllSeasons/img/bonoboLH-humanLH-viaTWD.gif

Syllabus Contents Cerebral Anatomy Cerebral Perfusion Imaging Radiopharmaceuticals Methodology Dosimetry Clinical Applications Cisternography Methods Pharmacokinetics

Brain SPECT and PET Radiopharmaceuticals

FDG PET/CT Tumor Cell Vascular Molecular Mechanism Glycogen Glycolysis Hexokinase K1 18FDG-6- phospho- glucono-lactone K3 18FDG 18FDG 18FDG-6P HMP shunt K4 K2 Glucose-6- phosphatase Uptake of FDG. FDG is a glucose analog that is taken up by metabolically active cells by means of facilitated transport via glucose transporters (Glut) in the cell membrane. In the cell cytoplasm, FDG undergoes phosphorylation to form FDG-6-phosphate (6P), which, unlike glucose, cannot undergo further metabolism and becomes trapped within the cell. N = nucleus. 18F-fru-6-P Glucose transporter protein Glycolysis

Tomographic perfusion image of the brain

Tomographic perfusion image of the brain

Tomographic perfusion image of the brain

Tomographic perfusion image of the brain

Normal cerebral perfusion

Abnormal Patterns Focal decreased uptake Focal increased uptake Crossed cerebellar diaschisis Enlargement of white matter or midline shift Structure disorder Abnormal distribution of the tracer cerebral atrophy Dissymmetric distribution

Clinical Indications of Brain Perfusion Imaging Cerebral ischemia Dementia Seizures Alzheimer diseases psychiatric diseases Brain death Parkinson's Disease

Clinical Applications of Brain Perfusion Imaging

Cerebral Vascular Diseases Acute CNS Ischemia/Infarction Transient Ischemic Attacks(TIA)

Acute CNS Ischemia/Infarction A focal or regional area of hypo- or absent perfusion on SPECT images. Larger defects area on SPECT than those noted on CT. The defects represent a combination of a central zone of infarction surrounded by a penumbra zone of ischemia but potentially  viable tissue.

Acute CNS Ischemia/Infarction(Cont.) Confirm the presence of cerebral infarction, monitor the effects of acute thrombolytic  therapy, and to predict stroke outcome . Higher sensitive than CT in the early (first 24 hours) detection of  acute ischemia, sensitivity 88-95% vs. 20-63% for CT, MRI has a sensitivity of about 80% for the detection of acute  infarction .

Subacute Phase Infarction Size of the infarct may be grossly underestimated due to luxury perfusion Luxury perfusion :uncoupling of flow and metabolism following an infarct. Apparently increased or normal tracer uptake despite the absence of metabolism in the involved area possibly related to either local breakdown in the blood-brain barrier or hyperemia from local tissue acidosis

Crossed Cerebellar Diaschisis

Transient Ischemic Attacks It occurs in 10 to 20% of stroke patients. One third of these patients suffer a stroke within 5 years without treatment.

Transient Ischemic Attacks(Cont.) Single or multiple cerebral blood perfusion defect or abscent Early detecting ischemia region with SPECT compared to CT or MRI. Sensitivity is about 55-60% with SPECT, the sensitivity declines with time. SPECT CBF stress test with Diamox has been shown to increase the likelihood of detection of residual blood flow changes after TIA.

Transient Ischemic Attacks

Epilepsy Epilepsy is one of the most prevalent neurological disorders.Seizures can be classified as either partial (focal) or generalized. Partial seizures originate in a given area of the brain and can be divided into simple (with no impairment of consciousness) and complex (with impairment of consciousness). About 10-20% of patients with partial complex seizures have inadequate control on medical treatment.Patients unresponsive to anti-convulsant therapy may be surgical candidates which can render the patient seizure free.

Epilepsy (Cont.) Scalp EEG often fails to accurately localize the seizure focus and although depth EEG is much more accurate, it is also extremely invasive and suffers from regional under sampling . CT and MRI have low sensitivity for seizure foci detection, 17% and 34% respectively. The role of brain SPECT is to localize the seizure focus.

Epilepsy (Cont.) Ictal Imaging: hyperperfusion at the seizure focus in 80 to 100% of patients. Crossed cerebellar hyperperfusion can also be identified in 75% of patients. Ipsilateral or diffuse cerebellar hyperperfusion may also be seen. Ipsilateral basal ganglia hyperperfusion is also common. Ictal SPECT: sensitivities 81 to 93%. The positive predictive value for localizing a unilateral seizure focus can be as high as 97% (when the tracer was injected immediately after the seizure).

Epilepsy (Cont.) Inter-ictal Imaging: Inter-ictal (seizure free) SPECT studies will demonstrate an area of diminished tracer activity (hypoperfusion) at the seizure focus in up to 50% of patients. Inter-ictal PET FDG studies demonstrate a focal area of hypometabolism in 60 to 70% of patients with normal MRI's. The area of hypometabolism is often much larger than the actual area of structural abnormality.

Epilepsy (Cont.) The sensitivity for localization of the ictus site using inter-ictal SPECT scanning ranges from 40 to 66%, which is less sensitive than post-ictal (70%) or ictal (80-90%) SPECT, and inter-ictal PET FDG (70%) imaging.

PATIENT PREPARATION Precautions - Pregnancy is a relative contraindication especially during 1st trimester. - Refrain from breastfeeding for 24 hrs for Tc-99m tracer and 2 hrs for FDG Pre-arrival : Patients should be instructed, if possible, to avoid caffeine, alcohol or other drugs known to affect cerebral blood flow (CBF) or glucose metabolism. Administration of psychoactive drugs should be avoided. If sedative drugs need to be considered, these should be administered not earlier than 5 min post-injection for Tc-99m radiopharmaceuticals and 15 minutes for FDG. For PET-FDG imaging, patients fast for at least 6 hours to allow the establishment of a metabolic steady state, a prerequisite for glucose metabolism evaluation.. Free access to water is allowed. All chronic medication should be maintained. Fasting advantageously diminishes FDG uptake by other organs than the brain and prevents high glucose plasma level, two causes of reduced PET-FDG image quality

PATIENT PREPARATION cont. Pre-Injection (a) patient cooperation. Keeping the patient informed about the whole procedure usually improves its cooperation. (b) Achieve a consistent environment during tracer injection and uptake: i. Place the patient in a quiet, dimly lit room, with ears unplugged. ii. eyes open ,not speak and not read.. iii. Ensure that the patient is seated or reclining comfortably. iv. Place intravenous access at least 10 min prior to injection to permit accommodation. Simultaneously for FDG-PET study, obtain a blood sample for determination of plasma glucose vi. Have no interaction with the patient prior to, during or up to 5 min post-injection for Tc-99m radiopharmaceuticals and 15 min for F-18 fluorodeoxyglucose. (c) Patients must be closely monitored at all times ; their neurologic deficits may require special care and monitoring.

Relevant patient data suggested for optimal interpretation of scans includes ● patient history, including : any past drug use or trauma, history of epilepsy, time and type of last seizure, recent brain surgery ● neurological examination ● psychiatrical examination, mental status examination ● interictal EEG for epilepsy ● recent morphologic imaging studies (e.g. CT, MRI) ● current medication and when last taken.

EEG monitoring EEG monitoring prior to and during the study may be required to exclude subclinical focal seizures in epileptic patients. Patients who are suspected to be unaware of partial seizures (and are thus unable to report their frequency or occurrence), require monitoring to assure that the study is indeed interictal. At least 20 minutes before injection and 10 minutes following the injection, no epileptic activity should be detectable on the EEG. Importantly, interictal CBF-SPECT and interictal FDGPET should be performed after a period of at least 24 hours without any clinical epileptic attack.

Time interval from injection to imaging For HMPAO and ECD, images obtained after a 20 min delay will be interpretable. For the best image quality allow for ≥90 min delay from injection for HMPAO and 45-60 min for ECD. For both tracers, imaging should be completed within 4 hr post-injection if possible. Excessive delay should be avoided. For FDG-PET, ≥30 min delay from injection to imaging is required for reaching a steady state.

Common Questions??????

Can a patient have a CT scan, diagnostic X ray examination or MRI scan on the same day as the PET/CT scan? Are there any radiation risks to other non-radiation workers, e.g. anaesthetists, para medical staffs, nurses? Can a patient breastfeed after a scan? Some of the administered 18F-FDG might be excreted in small amounts in breast milk. Normally, the scan should be delayed until breast feeding has stopped. But if the scan is needed urgently, then it is advisable to collect milk before the scan, so that this can be used to provide a feed after the scan. Furthermore, milk should be collected and discarded for 2 hours after the scan. Normal breast feeding can resume after that. 9. What if an ancillary staff member is in the early stage of pregnancy and is exposed to a patient who has undergone PET/CT? There is no significant risk involved in such an exposure No, there is no significant risk to the staff taking care of these patients. However, radiation from patients undergoing other diagnostic and therapeutic radionuclide procedures such as bone scans or radioiodine therapy may pose a risk of radiation exposure to medical staff and does require attention. Patients undergoing PET/CT scan would add to this radiation exposure. Following simple guidelines for reducing contact time and increasing distance would suffice to minimize the radiation exposure to staff. For patients with urinary catheters or incontinence, standard precautions for dealing with biohazardous material would be sufficient to prevent undue radiation exposure and contamination.

Can a patient breastfeed after a scan? Some of the administered 18F-FDG might be excreted in small amounts in breast milk. Normally, the scan should be delayed until breast feeding has stopped. But if the scan is needed urgently, then it is advisable to collect milk before the scan, so that this can be used to provide a feed after the scan. Furthermore, milk should be collected and discarded for 2 hours after the scan. Normal breast feeding can resume after that.

Is there significant risk to the staff taking care of these patients? What if an ancillary staff member is in the early stage of pregnancy and is exposed to a patient who has undergone PET/CT? There is no significant risk involved in such an exposure Is there significant risk to the staff taking care of these patients? No, there is no significant risk to the staff taking care of these patients. However, radiation from patients undergoing other diagnostic and therapeutic radionuclide procedures such as bone scans or radioiodine therapy may pose a risk of radiation exposure to medical staff and does require attention. Patients undergoing PET/CT scan would add to this radiation exposure. Following simple guidelines for reducing contact time and increasing distance would suffice to minimize the radiation exposure to staff. For patients with urinary catheters or incontinence, standard precautions for dealing with biohazardous material would be sufficient to prevent undue radiation exposure and contamination

rCBF changes during temporal lobe seizures

Epilepsy Ictal Inter-ictal

Interictal SPECT Brain Perfusion

Ictal SPECT Brain Perfusion

inter-ictal PET FDG

Extratemporal epilepsy Normal or inconclusive MRI is not unusual. Rapid rCBF changes. Short seizures are common. Need for very early injection Interictal SPECT has low sensitivity (30%) Ictal SPECT remains highly sensitive Guide for invasive EEG recording Subtraction images or SISCOM are required

SISCOM Improved localization, mostly in extratemporal epilepsy. Epileptogenic zone detected in 50% of patients with no localizing EEG and 76% with normal MRI Localizing SISCOM concordant with surgical site predicts successful surgery outcome (58% vs. 18% with non-localizing or non-concordant SISCOM).