Brain Perfusion Imaging Quiz

Radionuclide Imaging (RNI) - HTI 48102

• Focuses on brain and renal scans using radioactive materials
• RNI is the use of radioactive materials and cameras to detect the presence of disease or other conditions.
• Includes techniques such as planar brain imaging, SPECT, and PET imaging

Brain Scans - Central Nervous System

• Lateral ventricles are C-shaped structures beneath the cerebral cortex. They are usually symmetrical, but anatomical differences (one side larger than the other) occur in 5-12% of the population, often affecting the left side.
• The third ventricle is a narrow, funnel-shaped structure between the right and left thalamus, just above the brain stem.
• The fourth ventricle is diamond-shaped and runs alongside the brain stem. It has openings for cerebrospinal fluid (CSF) to drain.
• CSF flows through the ventricles, through interventricular foramina, then cerebral aqueduct, and finally draining into the central canal of the spinal cord.
• Choroid plexus within the lateral ventricle walls produces CSF.

Brain - Indications

• Planar brain imaging uses perfusion agents that don't cross the blood-brain barrier, often used for brain death studies.
• SPECT uses lipophilic radiopharmaceuticals that cross the blood-brain barrier to identify and localize normal or abnormal brain tissues/functions.
• This method shows regional cerebral blood flow (rCBF).
• PET imaging uses functional radiopharmaceuticals to reflect the metabolic and neurotransmitting events

Planar brain imaging - Radiopharmaceuticals

• Dynamic angiographic imaging uses bolus injection to rapidly image radiotracer arrival and measures cerebral perfusion. Radioactive material is used for imaging.
• 99mTc-DTPA (diethylenetriamine pentaacetic acid) and 99mTcO4 (pertechnetate) are radiopharmaceuticals commonly used.
• Delayed static (perfusion) imaging uses lipophilic agents and 99mTc-HMPAO (hexamethylpropyleneamine oxime) and 99mTc-ECD (ethylene l-cysteinate dimer) to measure tissue uptake and active functioning.

Blood Brain Barrier

• A barrier of brain capillaries that protect the brain from harmful circulating substances (toxins).
• Only water, gases and essential chemicals can penetrate.
• The integrity of the blood-brain barrier is vital for brain health and is compromised in some pathologies.

The principles of Brain RNI

• The blood-brain barrier (BBB) makes the brain a unique organ because neurons do not store oxygen and glucose metabolically. Thus, they require a constant supply and perfusion to maintain neuronal activities. The presence of the blood-brain barrier (BBB) is critical for proper brain function..
• Increased blood flow (perfusion) is a proxy for neuronal activity.
• Disruption of the BBB or absence of blood flow/perfusion can lead to pathological findings, especially brain death.

Planar cerebral imaging – 99mTc-DTPA

• 99mTc-DTPA is a common inexpensive chelator used for dynamic renal and brain imaging.
• 99mTc-DTPA undergoes rapid extravascular distribution swiftly.
• 99mTc-DTPA is cleared via glomerular filtration (in the kidneys).
• It has a low plasma protein binding which means it can cross the barrier into the organ easily.
• Radiation dose in terms of mSv is dependent on the body mass.

Patient positioning

• Patient positioning during brain scans should be as close as possible to the gamma camera.
• The patient should be in a supine position, during the imaging process.

Planar cerebral imaging – 99mTc-DTPA – Collimator, Dose, Imaging Setting, and Features

• Collimator: LEHR
• Patient position: Supine
• Dose: 15–30 mCi (555MBq – 1.11GBq)
• Dynamic image (Anterior view)
• Static image (Anterior, Posterior, and both Laterals (300k counts per view))
• Features: Symmetric perfusion, perfusion extending to calvarium convexity, and asymmetry that might arise from venous anatomical variations

Planar cerebral imaging – 99mTc-DTPA – Imaging Features

• Features: No apparent accumulation in brain tissue, overlying in scalp regions, and sinuses.

Planar cerebral imaging – 99mTc-DTPA – Indications

• Stroke (luxury perfusion)
• Brain tumor (as glioblastomas)
• Hemorrhage
• Cerebral vascular accidents

Brain Death scan - 99mTc-HMPAO

• Indications for brain death scanning: failure of components of neurologic examinations or test results are uncertain. If apnea test cannot be performed, to shorten duration of observation period, helps family understand, etc.

Epilepsy scan - 99mTc-HMPAO

• Epilepsy is a common neurologic disorder, with seizures classified as partial (focal) or generalized.
• 10–20% of patients experience inadequate seizure control even with treatments. This use of 99mTc-HMPAO is to discover and detect complex seizures.
• Depth EEG often shows better localization of seizure foci than scalp EEG. CT and MRI are generally less sensitive in detecting seizure foci.

Metabolic (tumor) imaging - 18F-FDG

• Collimator: PET
• Patient position: Supine
• Dose: 10–20 mCi (370–740 MBq)
• Imaging setting: 60 minutes after intravenous administration
• Preparation: fasting for 4+ hours, cessation of insulin, and a 30+ minute rest period
• CT scan necessary

Alzheimer's Disease

• Neurodegenerative disease causing brain atrophy, leading to severe memory loss (dementia) and cognitive decline.
• Causes are still unknown, but AD is a major issue in public healthcare.
• Early detection is critical but treatments are not currently available.

Cause of Alzheimer Disease - Amyloid hypothesis

• Aβ monomers become soluble oligomers, then insoluble fibrils (plaques), disrupting neurotransmission.
• Non-amyloidogenic pathway exists with α-secretase.
• Amyloidogenic pathway occurs with β-secretase.

AD diagnosis - Aß detection

• Aβ detection methods (PET) can flag early AD stages.
• Stages of detection on a chart include: Preclinical, Clinical, MCI and Dementia.

11C-PiB imaging

• 11C-PiB is a carbon-11-labeled compound that binds selectively to Aβ aggregates, allowing for detection using PET.
• The level of Aβ in patients is used to determine AD versus a healthy control.
• 11C-PiB imaging can identify differences in Aβ distribution (higher uptake in AD patients) and sensitivity is a key aspect of the test.

11C-PIB imaging – Aß distribution vs. MRI

• MRI and PET images show various levels of Aβ distribution in patients with and without Alzheimer's disease

18F-FBP imaging

• Shows Aβ distribution in gray matter regions.

AD imaging – the current available targets

• The available targets for AD imaging focus on Aβ and Tau to identify individuals at different disease stages.

Aβ imaging – not conclusive for AD diagnosis

• Despite various Aβ imaging agents, definitive diagnosis or effective treatment evaluation remains elusive.
• FDA cautions that negative scans can be interpreted against AD.

Tau Hypothesis

• Tau protein plays a critical role in maintaining microtubule stability in neuronal axons.
• Mutations or improper processing of tau proteins affect these processes, leading to hyperphosphorylation and aggregation, resulting in neurofibrillary tangles (NFTs) and eventual neuron damage, commonly associated with AD.

THK5117 imaging

• THK5117 detects tau protein distribution, which is particularly useful in AD imaging.
• The probe binds strongly to phosphorylated Tau (PHF-Tau).

AD imaging – FDG

• Detects decreased glucose metabolism in the brain that can reflect an abnormal condition, such as AD.
• Lower glucose uptake correlates with less active brain regions.

AD imaging – Tau protein signals (AV1451)

• AV1451 highlights variations in tau protein signal patterns to differentiate between healthy, mild cognitive impairment (MCI), and AD cases based on differing radiotracer accumulation levels through the brain. This is a possible method of earlier diagnosis.

Hurdles - Diagnostic value?

• Studies show variable results for amyloid, tau and TSPO tracers in AD and neuropathology, specifically for sensitivity, specificity and diagnostic discrimination.

AD research

• Some key AD research findings have been questioned by a study and, possibly, invalid or unreliable..

Renal Scan

• Assess renal function, acute renal failure and renal transplants.
• Glomerular filtration rate (GFR) is the volume of plasma that passes through the kidneys per unit time.
• An Effective renal plasma flow (ERPF) can be measured using PAH, a chemical substance that is cleared by the kidneys quickly, reflecting how effectively the kidneys are clearing substances from the blood.

Kidneys and the Urinary Tract

• Renal cortex: the outer layer of the kidney
• Renal medulla: the interior region of the kidney
• Glomerulus: filters blood within the kidney, for glomerular filtration.
• Nephron: responsible for filtering blood and forming urine/filtrate.
• Collecting duct (collecting tubules): carries the urine to the kidney pelvis before emptying it to the bladder.

Kidney Fact Sheet

• Excretory function of the kidneys involves passive filtration through the glomeruli for 20% and active secretion by the tubules for 80%.
• Normal GFR: 120 ml/min
• Effective renal plasma flow (ERPF): 600 ml/min
• Filtration fraction: 20%
• Two layers: cortex and medulla
• Approximate 20-25% of cardiac output flows through the kidneys, resting cardiac output is 5L/min, and resting kidney output is 1.2L/min.

Indications for Functional Studies

• Assessment of renal function
• Evaluation of a renal transplant
• Evaluation of acute renal failure

Renal Scintigraphy Positioning

• Supine position, posterior view preferred. Anterior can be used for unusual situations such as a horseshoe kidney, or when removing part of the bladder.

Glomerular Filtration Agents – 99mTc-DTPA

• Radioactive tracer 99mTc-DTPA is an inexpensive chelator used for dynamic renal and brain imaging.
• It has rapid extravascular and rapid distribution, cleared by glomerular filtration with low level (5-10%) plasma protein binding.
• It is used in perfusion imaging at the first pass, and delayed phase imaging.
• It has a radiation dose of 27 mSv/370 MBq at the bladder.

Tubular Secretion Agent – 99mTc-MAG3

• Radioactive tracer 99mTc-MAG3 is a hepatobiliary iminodiacetic acid comparable to Hippuran.
• The tracer is predominantly cleared by the proximal tubules (95%) by active secretion with minimal filtration. It has an extraction fraction of 40–50%, allowing better detection than 99mTc-DTPA.

Pharmacokinetics – 99mTc-MAG3

• The tracer is predominantly cleared via tubular secretion, improving renal plasma flow (ERPF) measurement accuracy.
• It exhibits minimal glomerular filtration (5%), making it suitable for patients with kidney insufficiency.
• Its higher extraction fraction (compared to 99mTc-DTPA) makes it preferred for renal function assessments or suspected obstructions.

Radiopharmaceuticals

• ERPF agents are completely removed from plasma during passage through the kidneys (high first-pass extraction).
• GFR agents are freely filterable by the glomeruli, not metabolized, and have little excretion through other organs.
• ERPF and GFR are clinically determined using plasma samples for high accuracy, or camera-based clearances.

Patient preparation for renal scans

• Hydration is required for consistent renal function study results.
• Patients must void their bladder before scans.
• Supine position is the usual study position.
• Large field of view (FOV) cameras and appropriate collimators are used in both standard and transplanted kidney cases.

Blood Flow Phase - Bolus Injection

• The study observes the arrival and presence of the radiotracer at the kidneys.
• A standard flow injection method is required for accurate identification.
• Post flow imaging is observed, with an increase in the flow through the kidney in about 4 to 8 minutes.

Blood Flow Phase - Transplanted Kidney

• This phase examines transplanted kidneys for proper vascular flow of the radiotracer.

Image Acquisition (Standard functional scan)

• The dose of radiotracer (99mTc-DTPA or 99mTc-MAG3) ranges between 100 and 370 MBq (10-40 mCi), based on specifics, etc.
• Functional imaging involves 3 phases: perfusion, parenchymal uptake and excretion, and collecting system patency.

Activity-time curve - Renogram

• Activity/time curves reflect the movement and uptake of radiotracers in the kidneys.
• Background ROIs are used to correct measurements from the kidney ROIs.

Image to the renogram

• The renogram curve shows an early, narrow peak, and then a plateau and excretion phase reflecting tracer passage.

Tubular Concentration Phase

• The curve represents the time it takes for the radiotracer to enter the tubules in the kidney.

Renogram - Reports

• Tmax (peak time): peak activity recorded in the kidney.
• T1/2 (excretion time): time needed to reduce activity by 50% from the maximum value.
• Mean Transit Time: average time for radiotracer passage through nephrons.
• Split Renal Function: percentage activity in each kidney, which shows the function status of each kidney.

GFR quantification

• Calculation methods use computational algorithms with counts collected from background activity using the time of arrival, body weight and height for accuracy.

Diuretic Renography - Indications

• Diagnoses obstructive (hydronephrosis) or non-obstructive (dilated collecting system) issues.

Diuretic Renography

• Furosemide (a diuretic) administration is utilized in studies for rapid clearance of the radiopharmaceutical, which aids in demonstrating renal function.
• Washout of radiotracer is absent with obstructive disease or when a significant amount of the radiotracer is retained within the dilated pelvis.

Diuretic Renography - Indications (Continued)

• Diagnoses vesicoureteral reflux, urinary tract infections, congenital malformations, previous obstructions, or noncompliant bladder complications

Indications for Morphological Studies

• Diagnoses acute pyelonephritis (inflammation of the kidney structure).
• Assesses parenchymal damage in acute and chronic pyelonephritis using quantitative measurements to distinguish disease severity.
• Identifies pediatric-related issues such as renal agenesis, ectopic kidneys, or horseshoe kidney formations

Renal Cortical Agent – 99mTc-DMSA

• A renal cortical imaging method utilizes the 99mTc-DMSA tracer.
• The agent is predominantly concentrated in the cortex for imaging analysis and only 10% is excreted in the urine.
• The long retention time for 99mTc-DMSA allows for more detailed cortical imaging compared to other renal tracers, particularly in the delayed phase where high-quality images are better obtained.

Pharmacokinetics – 99mTc-DMSA

• 40% of the tracer concentrates in the renal cortex approximately 6 hours after injection.
• Delayed imaging (higher SNR) at 1–3 hours is necessary, especially in individuals with reduced renal function

Image acquisition (Standard morphology scan)

• No specific patient preparation is required.
• 99mTc-DMSA (37 to 110 MBq [ ~ 1 to 3 mCi]) is administered intravenously.
• Imaging is done 2–4 hours after tracer administration.
• Large field-of-view (FOV) cameras with LEHR or pinhole collimators are used.
• RPO (right posterior oblique) and LPO (left posterior oblique) views are critical for visualization, or a SPECT scan may be necessary.

Renal Cortical Imaging – Morphology study

• Images are taken using pinhole collimators, providing better localization compared to parallel-hole collimators.

Renal Cortical Imaging – Pyelonephritis

• Homogeneous cortical uptake of DMSA in normal individuals.
• Three presentation patterns include focal, multifocal, or diffuse decreased activity.

Case – Suspected renal mass

• A 37-year-old woman had imaging/ultrasound testing to find 2.5-cm abnormalities in the interpolar region of the right kidney.
• MRI testing confirmed an abnormality that was equivocal to a mass versus normal hypertrophic columns of Bertin.
• 99mTc-DMSA was performed to supplement the MRI, combined analysis of the two tests helped achieve a final diagnosis.

Test your knowledge on brain perfusion imaging techniques, particularly focusing on the role of radiotracers like 99mTc-DTPA and 99mTc-HMPAO. This quiz covers essential concepts related to brain functionality, the blood-brain barrier, and preparation for brain imaging procedures. Prepare to dive deep into the nuances of cerebral imaging diagnostics.