Brain Perfusion Imaging Quiz

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Questions and Answers

What is a primary requirement for neurons due to their lack of intracellular metabolic stores?

Continuous supplies of amino acids

Continuous supplies of carbon dioxide

Continuous supplies of oxygen and glucose (correct)

Continuous supplies of fatty acids

What happens to brain functionality when there is disruption of the blood-brain barrier (BBB)?

Enhanced blood perfusion

Increased oxygen supply to neurons

Pathologic findings occur (correct)

Increased levels of glucose in the brain

What is the significance of 99mTc-DTPA in cerebral imaging?

It is primarily used for dynamic renal and brain imaging. (correct)

It has a long half-life and best suited for static imaging.

It is primarily a treatment for brain tumors.

It is only effective after a long period post-injection.

What is the consequence of having no blood flow/perfusion to the brain?

Brain death Signup and view all the answers

What is one of the pharmacokinetic properties of 99mTc-DTPA after injection?

Rapid extravascular distribution by vessel Signup and view all the answers

What is the recommended patient position during a brain perfusion scan?

Supine Signup and view all the answers

What is the role of the radiotracer in a brain perfusion scan?

To visualize blood flow and brain activity Signup and view all the answers

What should be emphasized to the patient before and during the brain perfusion scan?

The importance of immobility during imaging Signup and view all the answers

What type of imaging is used for assessing brain death?

Static imaging Signup and view all the answers

What is the typical dosage range for a brain perfusion scan with 99mTc-HMPAO?

15-30 mCi Signup and view all the answers

What background conditions should be standardized during a brain perfusion scan?

Ambient light and background noise Signup and view all the answers

Which abnormal conditions can a brain perfusion scan help diagnose?

Alzheimer's dementia Signup and view all the answers

What is a primary characteristic of the radiotracer used in brain perfusion scans?

It is lipophilic and penetrates the blood-brain barrier Signup and view all the answers

What is the primary function of the ventricles in the human brain?

Producing and secreting cerebrospinal fluid Signup and view all the answers

Which type of imaging uses lipophilic radiopharmaceuticals that cross the blood-brain barrier?

SPECT imaging Signup and view all the answers

What does dynamic angiographic imaging primarily measure?

Transient cerebral perfusion Signup and view all the answers

Which radiopharmaceutical is known for being used in delayed static imaging?

99mTc-HMPAO Signup and view all the answers

What type of imaging is typically performed for brain death studies?

Planar brain imaging Signup and view all the answers

What role does the foramen serve in brain anatomy?

Allows passage of cerebrospinal fluid Signup and view all the answers

What does SPECT imaging visualize?

Regional cerebral blood flow Signup and view all the answers

Which of the following is a characteristic of PET imaging?

It reflects metabolic and neurotransmitting events Signup and view all the answers

Which radiopharmaceutical is a measure of tissue uptake and active functioning within the brain?

99mTc-HMPAO Signup and view all the answers

What distinguishes lipophilic radiopharmaceuticals from others in brain imaging?

They routinely cross the blood-brain barrier Signup and view all the answers

What is the primary purpose of the imaging agents Vizamyl and Amyvid?

To assist in diagnosing early-onset Alzheimer's disease Signup and view all the answers

Which company developed the imaging agent Vizamyl?

Ohio-based GE Healthcare Signup and view all the answers

What type of imaging technique do Vizamyl and Amyvid utilize?

Positron Emission Tomography (PET) Signup and view all the answers

In what year did the FDA announce the approval of Vizamyl?

2014 Signup and view all the answers

What does the FDA's approval indicate about Vizamyl?

It has been validated as a diagnostic tool for Alzheimer's. Signup and view all the answers

Which PET imaging method is noted for its sensitivity in Alzheimer's disease diagnoses?

11C-PiB Signup and view all the answers

What does CSF Aβ1–42 indicate in the context of Alzheimer's disease diagnosis?

Amyloid deposition Signup and view all the answers

Which radiotracer is used specifically for tau imaging in Alzheimer's disease?

F-THK5105 Signup and view all the answers

Which of the following is associated with a positive correlation with dementia severity?

F-THK5105 retention Signup and view all the answers

What is the significance of elecetroencephalographic (EEG) findings in assessing Alzheimer’s disease?

Indicates neurodegeneration Signup and view all the answers

What type of changes are gray matter regions in the brain subjected to during Alzheimer's disease?

Amyloid diffusion Signup and view all the answers

Which factor does NOT contribute to Alzheimer's disease pathology?

Myelin integrity Signup and view all the answers

How does presymptomatic Alzheimer's disease relate to current imaging methods?

It is identifiable through amyloid-PET imaging. Signup and view all the answers

What does a high retention of tau PET tracer indicate in a patient suspected of having Alzheimer's disease?

Potential Alzheimer pathology Signup and view all the answers

What role does amyloid deposition play in Alzheimer’s disease progression?

It accelerates cognitive decline. Signup and view all the answers

What is the primary advantage of using Tau protein signals in AD imaging?

Higher signal-to-noise ratio (SNR) Signup and view all the answers

What does a higher signal-to-noise ratio (SNR) in imaging indicate?

Better clarity and accuracy in the images Signup and view all the answers

What is one of the hurdles associated with the diagnostic value of Tau PET imaging?

Difficulty in standardizing imaging protocols Signup and view all the answers

What aspect of Tau PET imaging is expected to improve in the future?

Enhanced imaging techniques and clarity Signup and view all the answers

Which of the following statements reflects the importance of Tau PET imaging in Alzheimer's disease (AD) research?

It provides insights into neurodegenerative changes associated with AD. Signup and view all the answers

Which factor can negatively influence the effectiveness of Tau PET imaging?

Presence of significant patient movement Signup and view all the answers

What role does the Tau protein play in the context of Alzheimer's disease?

It accumulates and forms tangles which disrupt neuronal function. Signup and view all the answers

Which imaging agent is commonly associated with Tau PET imaging for Alzheimer's disease evaluation?

AV1451 Signup and view all the answers

Study Notes

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.

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Description

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.