The Legacy of the TTASAAN Report—Premature Conclusions and Forgotten Promises: A Review of Policy and Practice Part I

Abstract

Brain perfusion single photon emission computed tomography (SPECT) scans were initially developed in 1970's. A key radiopharmaceutical, hexamethylpropyleneamine oxime (HMPAO), was originally approved in 1988, but was unstable. As a result, the quality of SPECT images varied greatly based on technique until 1993, when a method of stabilizing HMPAO was developed. In addition, most SPECT perfusion studies pre-1996 were performed on single-head gamma cameras. In 1996, the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (TTASAAN) issued a report regarding the use of SPECT in the evaluation of neurological disorders. Although the TTASAAN report was published in January 1996, it was approved for publication in October 1994. Consequently, the reported brain SPECT studies relied upon to derive the conclusions of the TTASAAN report largely pre-date the introduction of stabilized HMPAO. While only 12% of the studies on traumatic brain injury (TBI) in the TTASAAN report utilized stable tracers and multi-head cameras, 69 subsequent studies with more than 23,000 subjects describe the utility of perfusion SPECT scans in the evaluation of TBI. Similarly, dementia SPECT imaging has improved. Modern SPECT utilizing multi-headed gamma cameras and quantitative analysis has a sensitivity of 86% and a specificity of 89% for the diagnosis of mild to moderate Alzheimer's disease—comparable to fluorodeoxyglucose positron emission tomography. Advances also have occurred in seizure neuroimaging. Lastly, developments in SPECT imaging of neurotoxicity and neuropsychiatric disorders have been striking. At the 25-year anniversary of the publication of the TTASAAN report, it is time to re-examine the utility of perfusion SPECT brain imaging. Herein, we review studies cited by the TTASAAN report vs. current brain SPECT imaging research literature for the major indications addressed in the report, as well as for emerging indications. In Part II, we elaborate technical aspects of SPECT neuroimaging and discuss scan interpretation for the clinician.

The Legacy of the TTASAAN Report – Premature Conclusions and Forgotten Promises About SPECT Neuroimaging: A Review of Policy and Practice Part II

“…( 11 – 19 ). Similarly, as reviewed extensively in Pavel and colleagues ( 2 ), CT and MRI often miss areas of cortical dysfunction following concussion or TBI [e.g., Figure 4 in ( 2 )], while perfusion SPECT can readily detect TBI and differentiate TBI from control with a >95% accuracy ( 20 , 21 ).…”

“…This two-part series explores the policies and procedures related to perfusion SPECT functional neuroimaging and, ultimately, makes recommendations for revisions to the current policies and practices. In Part I, the comparison between the quality of the SPECT scans and the depth of the data for key neurological and psychiatric indications at the time of the TTASAAN report vs. the intervening 25 years were presented ( 2 ). We reviewed the research literature on traumatic brain injury (TBI) (encompassing over 24,000 subjects) and showed SPECT perfusion imaging is more sensitive that CT or MRI for detecting TBI.…”

“…We reviewed the use of perfusion SPECT in epilepsy, including the findings that ictal-interictal SPECT has an accuracy of 85.9% in localizing seizure foci. The vast field of neuroimaging in dementia was reviewed and perfusion SPECT was shown to have 96% sensitivity and 80% specificity in differentiating Alzheimer's disease (AD) from fronto-temporal dementia (FTD), comparable to fluorodeoxyglucose-positron emission tomography (FDG-PET) ( 2 , 3 ). Similarly, the conversion from mild cognitive impairment (MCI) to AD or FTD can be predicted with both perfusion SPECT and FDG-PET.…”

“…Similarly, the conversion from mild cognitive impairment (MCI) to AD or FTD can be predicted with both perfusion SPECT and FDG-PET. FDG-PET was found to predict the conversion from MCI to AD with a sensitivity of 70–90% and a specificity of 82.4–90%, while perfusion SPECT scans predict the conversion from MCI to AD with a sensitivity ranging from 89 to 97% and a specificity of 89–100% ( 2 ). In addition, we reviewed the SPECT neuroimaging research findings in neurotoxicity, attention-deficit hyperactivity disorder, depression, bipolar disorder, obsessive compulsive disorder, and stroke.…”

“…Functional neuroimaging is particularly vulnerable to technical errors or flaws. As discussed in Part I ( 2 ), an analysis of the validity of fMRI post-processing methods has revealed significant flaws which potentially invalidate many fMRI studies and the resulting conclusions about fMRI findings in certain conditions ( 6 ). The American Psychiatric Association has questioned the value of fMRI research into psychiatric disorders ( 7 ).…”