Detection of Thirty-Second Cognitive Activations in Single Subjects with Positron Emission Tomography: A New Low-Dose H215O Regional Cerebral Blood Flow Three-Dimensional Imaging Technique

Positron emission tomography regional CBF (rCBF) studies of cognitive processes have traditionally required 30–60 mCi of H215O per scan and intersubject averaging to achieve statistical significance. However, intersubject anatomical, functional, and disease variability can make such an approach problematic. A new method that produces significant results in single subjects is presented. It is based upon high-sensitivity three-dimensional imaging and a “slow” bolus administration of >15 mCi of H215O per scan. The method is validated in four normal volunteers using control and auditory-language activation tasks with four scans per condition and statistical parametric mapping analysis. It is demonstrated that the rCBF distribution associated with the cognitive state is detected during the arrival of radiotracer in the brain. This occurs over 30 s and constitutes a critical temporal window during which stimulation should be performed. A 90-s acquisition time is found to produce results of greater significance than a 60-s acquisition time. The implications of the results and the functional neuroanatomical findings are discussed. This method is suitable for the study of individual functional neuroanatomy in many neuropsychological, pharmacologic, and symptom states in normal subjects and in patients with psychiatric and neurologic disorders.

[1]  M E Raichle,et al.  Evidence of the Limitations of Water as a Freely Diffusible Tracer in Brain of the Rhesus Monkey , 1974, Circulation research.

[2]  K M Heilman,et al.  Auditory affective agnosia. Disturbed comprehension of affective speech. , 1975, Journal of neurology, neurosurgery, and psychiatry.

[3]  P E Roland,et al.  Focal activations of human cerebral cortex during auditory discrimination. , 1981, Journal of neurophysiology.

[4]  James L. McClelland,et al.  An interactive activation model of context effects in letter perception: I. An account of basic findings. , 1981 .

[5]  J C Mazziotta,et al.  Tomographic mapping of human cerebral metabolism , 1982, Neurology.

[6]  T. Olsen,et al.  Left-right cortical asymmetries of regional cerebral blood flow during listening to words. , 1982, Journal of neurophysiology.

[7]  G. Ojemann Ojemann's data: Provocative but mysterious , 1983, Behavioral and Brain Sciences.

[8]  M. Raichle,et al.  Brain blood flow measured with intravenous H2(15)O. I. Theory and error analysis. , 1983, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[9]  M. Mintun,et al.  Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation. , 1983, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[10]  D A Rottenberg,et al.  Accuracy of PET RCBF measurements: effect of time shift between blood and brain radioactivity curves. , 1986, Physics in medicine and biology.

[11]  I. Kanno,et al.  Error Analysis of a Quantitative Cerebral Blood Flow Measurement Using H215O Autoradiography and Positron Emission Tomography, with Respect to the Dispersion of the Input Function , 1986, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[12]  R A Koeppe,et al.  Examination of assumptions for local cerebral blood flow studies in PET. , 1987, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[13]  F Shishido,et al.  A System for Cerebral Blood Flow Measurement Using an H215O Autoradiographic Method and Positron Emission Tomography , 1987, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[14]  James L. McClelland,et al.  An interactive activation model of context effects in letter perception: part 1.: an account of basic findings , 1988 .

[15]  M. Posner,et al.  Localization of cognitive operations in the human brain. , 1988, Science.

[16]  P. T. Fox,et al.  Positron emission tomographic studies of the cortical anatomy of single-word processing , 1988, Nature.

[17]  Karl J. Friston,et al.  Localisation in PET Images: Direct Fitting of the Intercommissural (AC—PC) Line , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  Michael E. Phelps,et al.  The C15O2 Build-up Technique to Measure Regional Cerebral Blood Flow and Volume of Distribution of Water , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  P T Fox,et al.  A Highly Accurate Method of Localizing Regions of Neuronal Activation in the Human Brain with Positron Emission Tomography , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[20]  T. Spinks,et al.  Noise Equivalent Count Measurements In A Neuro-pet Scanner With Retractable SEPTA , 1990, 1990 IEEE Nuclear Science Symposium Conference Record.

[21]  Karl J. Friston,et al.  The Relationship between Global and Local Changes in PET Scans , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  D L Bailey,et al.  Fully Three-dimensional Reconstruction For A Pet Camera With Retractable Septa , 1990, 1990 IEEE Nuclear Science Symposium Conference Record.

[23]  M M Mesulam,et al.  Large‐scale neurocognitive networks and distributed processing for attention, language, and memory , 1990, Annals of neurology.

[24]  E. Hoffman,et al.  Measuring PET scanner sensitivity: relating countrates to image signal-to-noise ratios using noise equivalents counts , 1990 .

[25]  Karl J. Friston,et al.  Comparing Functional (PET) Images: The Assessment of Significant Change , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[26]  D. Chadwick,et al.  Exploring brain functional anatomy with positron tomography. , 1991, Ciba Foundation symposium.

[27]  E. Hoffman,et al.  Fully three-dimensional reconstruction for a PET camera with retractable septa , 1991 .

[28]  R. Duckrow Regional Cerebral Blood Flow during Spreading Cortical Depression in Conscious Rats , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[29]  Ciba Foundation Symposium 163 - Exploring Brain Functional Anatomy with Positron Tomography , 1991 .

[30]  Karl J. Friston,et al.  Distribution of cortical neural networks involved in word comprehension and word retrieval. , 1991, Brain : a journal of neurology.

[31]  Karl J. Friston,et al.  Regional cerebral blood flow during volitional breathing in man. , 1991, The Journal of physiology.

[32]  Karl J. Friston,et al.  A direct demonstration of functional specialization in human visual cortex , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[33]  Karl J. Friston,et al.  A PET study of word finding , 1991, Neuropsychologia.

[34]  I Kanno,et al.  Rapid measurement of cerebral blood flow with positron emission tomography. , 1991, Ciba Foundation symposium.

[35]  P T Fox,et al.  Does inter-subject variability in cortical functional organization increase with neural 'distance' from the periphery? , 1991, Ciba Foundation symposium.

[36]  M. Gilardi,et al.  Noise Equivalent Count Measurements In A Neuro-pet Scanner With Retractable SEPTA , 1990, 1990 IEEE Nuclear Science Symposium Conference Record.

[37]  Richard S. J. Frackowiak,et al.  The anatomy of phonological and semantic processing in normal subjects. , 1992, Brain : a journal of neurology.

[38]  M. Posner,et al.  Attentional Mechanisms and Conscious Experience , 1992 .

[39]  T J Spinks,et al.  Physical performance of a positron tomograph for brain imaging with retractable septa. , 1992, Physics in medicine and biology.

[40]  Alan C. Evans,et al.  Lateralization of phonetic and pitch discrimination in speech processing. , 1992, Science.

[41]  J. Mazziotta,et al.  Rapid Automated Algorithm for Aligning and Reslicing PET Images , 1992, Journal of computer assisted tomography.

[42]  Richard S. J. Frackowiak,et al.  Area V5 of the human brain: evidence from a combined study using positron emission tomography and magnetic resonance imaging. , 1993, Cerebral cortex.