Notes on PET Imaging in Neurology

PET Imaging in Neurology

  • Speaker: Karl F. Hubner, Department of Radiology, University of Tennessee Medical Center, Knoxville, Tennessee
  • Article Context: This is the third article in a four-part series on PET imaging.
  • Learning Objectives: Upon completion of this article, the reader should be able to:
    • Identify radiotracers used in neuro-PET imaging.
    • Understand the technical considerations involved in neuro-PET imaging.
    • Recognize the practical applications of neuro-PET imaging.

Overview of PET Imaging

  • Definition: Positron emission tomography (PET) imaging is a non-invasive physiological imaging technique that allows observation of metabolic and biochemical changes in the human brain as it performs its functions.
  • Historical Background: Initially used for examining the brain, PET imaging has evolved from a research tool to a clinically applicable diagnostic imaging modality, now including applications in cardiology and oncology.
  • Previous Articles: The first article in this series provides a history, technical aspects of radiotracer production, instrumentation, and an overview of PET utility.
  • Current Focus: This article focuses on applications of PET in patients with:
    • Complex partial epilepsy.
    • Cerebrovascular disease.
    • Dementia.
    • Brain tumors.
    • Brief discussion on mental functional illnesses and the development of PET applications in this area.

Neuro-PET Technology

Radiotracers for Neuro-PET Studies

  • Biochemical Parameters Measured:
    • Cerebral blood flow (CBF).
    • Cerebral metabolic rate of glucose (cmRGlc).
  • Key Relationships: Strong correlation exists among brain function, CBF, and metabolism.
  • Tracer Kinetic Models: Established and validated for measuring CBF and cmRGlc using advanced PET instruments.
  • Methods of Conducting CBF Studies:
    • H2 150 Method: Involves intravenous bolus injection.
    • C15O2 Method: Involves inhalation at steady state; technically complex with considerations on radiation doses.
    • Use of nitrogen-13 labeled ammonia is common in CBF studies.
Cerebral Glucose Metabolism
  • Radiotracers:
    • [18F]-2-deoxyglucose (FDG): Preferred agent due to a convenient half-life of 110 minutes.
    • [11C]-2-deoxyglucose: Shorter half-life of 20 minutes, more physiologic but enters complex metabolic pathways, complicating analysis.
  • Image Acquisition: Typically starts 40-45 minutes post injection of radiotracer.
Oxygen Metabolism
  • Measurement: Determined through the cerebral extraction of inhaled O2, total arterial oxygen content, and CBF; complex logistics restrict routine application.
Amino Acid Transport and Protein Synthesis
  • Studied Amino Acids: Includes L-methionine, L-leucine, DL-tryptophan, several unnatural amino acids.
  • Labels Used for Studies: L-leucine and L-phenylalanine with 11C for measuring protein synthesis rates.
  • pH Measurement: Research application using 11C-dimethyloxazolidinedione (DMO); currently lacks clinical utility.
  • Radioligands: Used for PET neuroreceptor studies and are still in research phases.

Patient Preparation for Neuro-PET Studies

  • Importance of Patient Condition: Required to measure differences in blood flow, metabolism, or neurochemical relationships across brain regions.
  • Research Findings: Activation of brain areas leads to increased glucose uptake, thus the need for control over external conditions (noise, temperature, light).
  • Preparation Protocol:
    1. NPO for 4 hours prior to the PET scan.
    2. Patient hydration is essential.
    3. Quiet waiting/prep area for 15-30 minutes before scanning.
    4. Initiate intravenous (i.v.) access with a 20-gauge intracath.
    5. Start slow i.v. drip of normal saline.
    6. Ensure patient comfort until scanning.
    7. Avoid sedation when possible.

Performing a PET Brain Scan

  • Procedure Steps:
    • Position the patient properly for scanning.
    • Conduct a transmission scan with an external source for attenuation correction.
    • Radiotracer injection followed by emission scanning, either immediately or after an appropriate interval post-injection.
  • Data Collection: Requires multiple arterial blood samples for kinetic model input functions and to quantify metabolic rates.

Quantitation of PET Data

  • Tracer Kinetic Models: Necessary for measuring metabolic rates.
  • Analytical Complexity: The trade-off between the complexity required for research versus clinical application. Possible methods include:
    • Strict tracer kinetic methods for research settings.
    • Simpler methods like the graphic method by Patlak or dynamic methods based on activity concentration ratios.
  • Data Analysis Tasks:
    • Compare average counts from regions of interest (ROI).
    • Produce sequential activity distribution profiles from PET studies.
    • Calculate differential absorption ratios (DAR) for dynamic studies.

Practical PET Applications for Neurologic Disorders

Complex Partial Epilepsy

  • Context: Approximately 800,000 epileptics in the U.S. are resistant to therapy; PET imaging aids in identifying epileptogenic foci.
  • Clinical Utility of PET:
    • Increases sensitivity for locating foci when CT and MRI appear normal.
    • Dr. Jerome Engel Jr. pioneered the use of PET for surgical treatment selection in partial epilepsy.
    • Increased CBF and glucose metabolism observed in epileptogenic foci during seizures, with decreased metabolite levels interictally.
    • High sensitivity levels observed (approximately 70%), increased sensitivity with opiate receptor density assessment using 11C-Carfentanil.

Cerebrovascular Disease (Stroke)

  • Application of PET: Used to assess strokes through CBF and glucose metabolism, aiding prognosis and rehabilitation planning.
  • Findings: Matching scans indicate decreased blood flow and metabolism, with implications on tissue viability and treatment options (e.g., endarterectomy).
  • Diamox Administration: Used to test vasodilatory responses, informing therapeutic decisions in cases of carotid artery occlusion.

Dementias

  • Characteristic Patterns in Alzheimer's Disease (AD): Glucose utilization patterns observed in affected brain regions (parietal lobes, temporal lobes, occipital lobes, etc.).
  • Diagnostic Limitations: PET cannot definitively diagnose AD; normal uptake patterns observed in depression-related dementia.

Brain Tumors

  • Clinical Use of PET: Accepted for grading, monitoring treatment responses, and differentiating tumor types.
  • Common Radiotracers:
    • [18F]FDG: Standard for metabolic activity correlation with tumor grade.
    • [11C]-L-methionine: Possible sensitivity for tumor proliferation detection.
    • 11C-ACBC: Emerged as a more effective tracer for highlighting tumor-associated amino acid uptake.
  • Example Case: PET studies comparing MRI with different radiotracers to differentiate between tumor recurrence and radiation necrosis.

PET Applications in Neuropsychiatric Disorders

  • Potential Uses: Can map receptors in the brain using specific ligands for diagnostic insights into psychiatric conditions.
  • Challenges: Variability in environmental factors complicates clear interpretation. Patterns observed include:
    • Normal glucose metabolism in schizophrenia.
    • Global depression of metabolic rates in unipolar/bipolar disorders.
    • Increased FDG uptake in compulsive-obsessive disorder cases.
  • Current Status: Routine PET scans for psychiatric diagnoses are emerging but still limited, with expected advancements noted in the context of ongoing research.

Conclusion

  • Evolution of PET Imaging: Shifted from research to clinical applicability in both intracranial and extracranial diseases.
  • Validation: Several PET applications for treating neurologic disorders are now accepted as clinically valuable, although PET’s role in understanding functional mental illness still requires further exploration.

Acknowledgments

  • Thanks to Kathy Hunter, CNMT, Don Cipriano, CNMT, Valerie Hendrix, and Cassandra Young for technical and manuscript preparation assistance.