Monte S. Buchsbaum, M.D.Professor of Psychiatry

Director, Neuroscience PET Laboratory

New York

Use and admissibility of positron emission tomography (PET) scanning in head injury

Anatomy and function

PET fluorodeoxyglucose

• Uptake of artificial radiolabeled sugar (FDG) over 30 minutes

• Subject does task during uptake

• FDG metabolically trapped in brain

• Move to scanner after uptake to image brain activity during task

After uptake, subject lies in scanner

PET shows abnormalities in:

• Head injury

• Schizophrenia

• Alzheimer’s disease

• Stroke

• Chronic methamphetamine abuse

Visualizing brain injury

• Computerized tomography (CT)

• Magnetic resonance imaging (MRI)

• Single photon emission computed tomography (SPECT)

• Electroencephalographic mapping

• Positron emission tomography (PET)

Head injury by dropping at delivery

Head injury after birth

Statistical probability map

Statistical probability map

Normal group mean=1.20standard deviation .10lower limit of normal=1.00

Patient value=0.90

Frontal lobe damage• lack of insight

• disinhibition

• loss of mental models of social rules

Automobile head injury

Frontal lobe

Closed head injury imaging

• “The most promising aspects of the application of nuclear medicine techniques …relate to the demonstration of neuronal dysfunction in regions that look structurally intact on CT or MRI”

• Oder et al.

Semin Nucl Med. 2003 Apr;33(2):136-47.

Newberg AB, Alavi A.

Division of Nuclear Medicine, Philadelphia, PA 19104, USA.

Neuroimaging techniques provide some of the most important diagnostic, prognostic, and pathophysiological information in the management of brain injury. Anatomical imaging modalities can help assess intracranial hemorrhage, fractures, and other structural lesions. Functional imaging has been shown to be helpful in assessing the areas of the brain affected by the trauma as well as determining long term prognosis and rehabilitation potential. This article will review the current uses of neuroimaging techniques in head trauma and delineate future applications.

Semin Nucl Med. 2003 Apr;33(2):136-47

Van Heertum et al.

• In evaluating acute head injury, CT and MR are the primary diagnostic tools. They play a critical role in detecting intracranial lesions that may require neurosurgical intervention. It should be noted, however, that SPECT and PET brain imaging have been found to be better than CT or MRI as prognostic indicators and thus may play a valuable role in the critical care management of these patients. In general, patients with larger and or more numerous lesions encountered on SPECT or PET relative to CT or MRI tend to have a poorer prognosis and conversely an initial negative

Seminars in Nuclear Medicine 34:300 2004

Closed head injury

• “The PET scans in each study demonstrated cerebral pathology not visualized by CT and in some cases, not visualized by MRI, either.

Boller et al. Annals New York Academy of Sciences, 769:23, 1995

Skull fracture, orbital surface

Encephalomalacia on MRI

Typical adult and patient

ab

PET and statistical analysis

PET and MRI

MRI PET statistics

Closed head injury

• “The PET scans in each study demonstrated cerebral pathology not visualized by CT and in some cases, not visualized by MRI, either.

Boller et al. Annals New York Academy of Sciences, 769:23, 1995

Subtraction of right from left in severe hemispheric injury

Left minus right of patient minus mean normal score/normal sd

Left minusRight 2 sd low

Statistical survey of brain

Basal ganglia and temporal lobe

Temporallobe

Basal ganglia

Mitigative evidence• Brain change associated with mental

illness

• brain damage to executive functions

• brain damage to areas involved in impulse control

• brain diseases diminishing capacity for cognitive function

Head injury in a violent offender

Multiple regions of decreased function

Two head injuries before crime

Patient AB

Competency

Gigante statistical contrast

Patient and areasin lowest 5% of elderly

33 patients with AD statistically contrasted with33 normal elderly

Regression95% confid.

Prediction of Patient MMSE Score from PETScattergram of 31 patients at various stages of AD

Correlation: r = .42123 p < 0.05

Relative Glucose Metabolic Rate in Right Temporal Lobe

MM

SE

Sco

re

10

14

18

22

26

30

0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4

VG

Scientific basis of PET

• More than 5000 scientific articles in reviewed journals

• 18-F deoxyglucose widely accepted as valid and reliable assessment of metabolic rate

• Quantitative analysis on pixel-by-pixel basis widely used in hundreds of research studies

PET has wide scientific base

Research tools may receive more detailed scientific scrutiny than clinical tools

Scientific basis of PET• Insurance coverage is not a measure of

scientific acceptability

• 18-F deoxyglucose widely accepted in the scientific community for assessment of metabolic rate and regional brain function

• Insurance pays for Alzheimer’s disease vs. Picks disease since it changes treatment, not confirms untreatable diagnosis

Scientific basis of PET

• 18-F deoxyglucose widely accepted for assessment of metabolic rate and regional brain function

• DNA testing is widely accepted as forensic evidence but is not paid for by insurance because it doesn’t affect patient care

Diagnosis and lab measures

• Diagnosis requires history, physical examination and laboratory tests

• Few diagnoses are made on the basis of a single laboratory test

• PET helps corroborate history and physical examination

Diagnosis and lab measures

• Validation based on scientific principle

• Watch for “too few scientific articles on PET scans in this disease in this type of patient at this age…”

• PET helps corroborate history and physical examination

Exclusion of evidence

• More often rejected on non-disclosure than scientific merit

• Disclose displays, especially normal images

• Specify what material was used to arrive at opinion of experts to avoid unreasonable requests for information and data

“just for research”

• Research published in peer-reviewed journals

• Research requires statistical confirmation

• Clinical usage may not always be supported by rigorous research

• Insurance may be paid for tests not supported by research

Admissibility in New York

R 4532-a. X-rays, magnetic resonance images, computed axial tomograms, positron emission tomographs,electromyograms, sonograms and fetal heart rate monitorstrips in personal injury actions

Admissible if photographically identified, disclosed 10 days before the date of trial

Amended CPLR 4532, May 23, 1986

Kelly/Frye RulePeople v. Kelly (1976) 17 Cal.3d 24

• The scientific method must have been shown to be reliable

• The witness utilizing the new procedure must be qualified as an expert in the field

• It must be shown that correct scientific procedures were used in the application of the new procedure (summary by Terri Towery Feb 18, Monterey Capital Case Conference)

Diminished frontal lobe function

We found these two in the group of normals

Two standard deviations means just that…below 5% of the population

Diffusion tensor imaging

Whitematter ofCorpuscallosum

Monte S. Buchsbaum, M.D.Mount Sinai School of Medicine

212-241-5294

monte.buchsbaum@mssm.edu

Temporal lobe change

Pt. JH

Parietal lobe metabolic decrease

Nat Neurosci 1999 Nov;2(11):1032-7

Impairment of social and moral behavior related to early damage in human prefrontal cortex.

Anderson SW, Bechara A, Damasio H, Tranel D, Damasio AR

The long-term consequences of early prefrontal cortex lesions occurring before 16 months were investigated in two adults. The two early-onset patients had severely impaired social behavior despite normal basic cognitive abilities, and showed insensitivity to future consequences of decisions. Unlike adult-onset patients, however, the two patients had defective social and moral reasoning, suggesting that the acquisition of complex social conventions and moral rules had been impaired.

A man infected with cholera is not allowed to mix freely with the population, but we do not

think him wicked. We may similarly be obliged to interfere with the freedom of a

murderer, but we should not have a feeling of moral reprobation in the one case more than in

the other.

Bertrand Russell

Aging change

Performance on CPT task during FDG uptake

• Murderers 3.6 SD= 0.71

• Controls 3.5 SD =0.77

Neurology 1998 Jul;51(1):142-8 Clinicometabolic dissociation of cognitive functions and social behavior in frontal lobe lesions.

Sarazin M, Pillon B, Giannakopoulos P, Rancurel G, Samson Y, Dubois B

Case studies suggest a dissociation between cognitive functions that have been impaired after damage to the dorsolateral prefrontal cortex and social skills disturbed when the ventromedial prefrontal areas are affected. Because this dissociation had not been confirmed in a clinical setting, clinicometabolic PET correlations were sought in 13 patients with various lesions of the prefrontal cortex.: Executive-function test performance was significantly correlated with activity in the dorsolateral prefrontal cortex) and anterior cingulate cortex. Behavioral scores were significantly correlated with activity in the frontopolar and orbitofrontal cortex.