Michael D. Devous

Brain Functional Localization: A Survey of Image Registration Techniques

Functional localization is a concept which involves the application of a sequence of geometrical and statistical image processing operations in order to define the location of brain activity or to produce functional/parametric maps with respect to the brain structure or anatomy. Considering that functional brain images do not normally convey detailed structural information and, thus, do not present an anatomically specific localization of functional activity, various image registration techniques are introduced in the literature for the purpose of mapping functional activity into an anatomical image or a brain atlas. The problems addressed by these techniques differ depending on the application and the type of analysis, i.e., single-subject versus group analysis. Functional to anatomical brain image registration is the core part of functional localization in most applications and is accompanied by intersubject and subject-to-atlas registration for group analysis studies. Cortical surface registration and automatic brain labeling are some of the other tools towards establishing a fully automatic functional localization procedure. While several previous survey papers have reviewed and classified general-purpose medical image registration techniques, this paper provides an overview of brain functional localization along with a survey and classification of the image registration techniques related to this problem

β-Amyloid burden in healthy aging Regional distribution and cognitive consequences

Objective: Several lines of evidence suggest that pathologic changes underlying Alzheimer disease (AD) begin years prior to the clinical expression of the disease, underscoring the need for studies of cognitively healthy adults to capture these early changes. The overall goal of the current study was to map the cortical distribution of &bgr;-amyloid (A&bgr;) in a healthy adult lifespan sample (aged 30–89), and to assess the relationship between elevated amyloid and cognitive performance across multiple domains. Methods: A total of 137 well-screened and cognitively normal adults underwent A&bgr; PET imaging with radiotracer 18F-florbetapir. A&bgr; load was estimated from 8 cortical regions. Participants were genotyped for APOE and tested for processing speed, working memory, fluid reasoning, episodic memory, and verbal ability. Results: A&bgr; deposition is distributed differentially across the cortex and progresses at varying rates with age across cortical brain regions. A subset of cognitively normal adults aged 60 and over show markedly elevated deposition, and also had a higher rate of APOE ε4 (38%) than nonelevated adults (19%). A&bgr; burden was linked to poorer cognitive performance on measures of processing speed, working memory, and reasoning. Conclusions: Even in a highly selected lifespan sample of adults, A&bgr; deposition is apparent in some adults and is influenced by APOE status. Greater amyloid burden was related to deleterious effects on cognition, suggesting that subtle cognitive changes accrue as amyloid progresses. GLOSSARY: A&bgr;: &bgr;-amyloid AD: Alzheimer disease DLBS: Dallas Lifespan Brain Study DLPFC: dorsolateral prefrontal cortex ETS: Educational Testing Service FWHM: full width at half maximum GLM: general linear model MCI: mild cognitive impairment OFC: orbital-frontal cortex ROI: region of interest SUVR: standardized uptake value ratio WAIS: Wechsler Adult Intelligence Scale

SPECT perfusion imaging in the diagnosis of Alzheimer's disease: a clinical-pathologic study.

Objective: Numerous studies have suggested that temporoparietal hypoperfusion seen on brain imaging with SPECT may be useful in diagnosing AD during life. However, these studies have often been limited by lack of pathologic validation and unrepresentative samples. The authors performed this study to determine whether SPECT imaging provides diagnostically useful information in addition to that obtained from a clinical examination. Methods: Clinical data and SPECT images were collected prospectively, and patients were followed to autopsy. Clinical history, pathologic findings, and SPECT images were each evaluated by raters blind to other features, and clinical and SPECT diagnoses were compared with pathologic diagnoses. The study population consisted of 70 patients with dementia, followed to autopsy; 14 controls followed to autopsy; and 71 controls (no autopsy performed). The primary outcome was the likelihood of a pathologic diagnosis of AD given a positive clinical diagnosis, a positive SPECT diagnosis, and both. Results: When all participants (patients and controls) were included in the analysis, the clinical diagnosis of “probable” AD was associated with an 84% likelihood of pathologic AD. A positive SPECT scan raised the likelihood of AD to 92%, whereas a negative SPECT scan lowered the likelihood to 70%. SPECT was more useful when the clinical diagnosis was “possible” AD, with the likelihood of 67% without SPECT, 84% with a positive SPECT, and 52% with a negative SPECT. Similar results were found when only patients with dementia were included in the analysis. Conclusions: In the evaluation of dementia, SPECT imaging can provide clinically useful information indicating the presence of AD in addition to the information that is obtained from clinical evaluation.

Hypofrontality and cognitive impairment in schizophrenia: Dynamic single-photon tomography and neuropsychological assessment of schizophrenic brain function

Regional cerebral blood flow (rCBF) was assessed in 40 chronic male schizophrenic patients (20 medicated, 20 unmedicated) and 31 matched normal controls with Dynamic Single-photon Emission Computed Tomography (D-SPECT). Blind analyses of normalized color-coded tomograms revealed significant bifrontal and bitemporal rCBF deficits in the patient group. Frontal flow deficits were most prominent in paranoid patients (n = 21) and right temporal deficits were most prominent in nonparanoid patients (n = 19). These relative regional declines were observed within the context of significantly elevated hemispheric blood flow in schizophrenics compared with controls. Reduced left frontal rCBF was associated with neuropsychological impairment on the Wisconsin Card Sorting Test and Luria-Nebraska Battery. Increased hemispheric CBF was correlated with the presence of positive schizophrenic symptoms. Medication status was unrelated to rCBF. These findings demonstrate that hypofrontality has important implications for cognitive function in some schizophrenic individuals.

Diffusion tensor tractography of traumatic diffuse axonal injury.

BACKGROUND Diffuse axonal injury is a common consequence of traumatic brain injury that frequently involves the parasagittal white matter, corpus callosum, and brainstem. OBJECTIVE To examine the potential of diffusion tensor tractography in detecting diffuse axonal injury at the acute stage of injury and predicting long-term functional outcome. DESIGN Tract-derived fiber variables were analyzed to distinguish patients from control subjects and to determine their relationship to outcome. SETTING Inpatient traumatic brain injury unit. PATIENTS From 2005 to 2006, magnetic resonance images were acquired in 12 patients approximately 7 days after injury and in 12 age- and sex-matched controls. MAIN OUTCOME MEASURES Six fiber variables of the corpus callosum, fornix, and peduncular projections were obtained. Glasgow Outcome Scale-Extended scores were assessed approximately 9 months after injury in 11 of the 12 patients. RESULTS At least 1 fiber variable of each region showed diffuse axonal injury-associated alterations. At least 1 fiber variable of the anterior body and splenium of the corpus callosum correlated significantly with the Glasgow Outcome Scale-Extended scores. The predicted outcome scores correlated significantly with actual scores in a mixed-effects model. CONCLUSION Diffusion tensor tractography-based quantitative analysis at the acute stage of injury has the potential to serve as a valuable biomarker of diffuse axonal injury and predict long-term outcome.

Normal Distribution of Regional Cerebral Blood Flow Measured by Dynamic Single-Photon Emission Tomography:

Regional CBF (rCBF) was measured quantitatively using the inert-gas washout technique with xenon-133 and single-photon emission computed tomography. Tomographic data were reconstructed by filtered back projection, and flow was calculated according to the double-integral method. Ninety-seven subjects ranging in age from 20 to 59 years received a single examination; eight of these received a second examination within 1 h of the first; seven others received a second examination separated from the first by 1–10 days. Transverse-section images were obtained at 2, 6, and 10 cm above and parallel to the canthomeatal line (CML). Cortical gray matter flows were obtained from 12 brain regions in the slice 6 cm above the CML, and cerebellar and inferior cerebral gray matter flows were obtained from 4 regions in the slice 2 cm above the CML. Mean gray matter flow was 72 ± 12 ml/min/100 g, with highest flows in the parietal lobes and visual cortex. No significant differences in rCBF occurred when a second study followed the first by 30 min to 10 days. Right-sided rCBF was slightly higher than left in all regions except frontal and parietal lobes where there was no difference. Flow was higher in women than in men and declined mildly with age for both sexes (slope = −0.33 ml/min/100 g/year; p < 0.05).

Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages

SEE THAL AND VANDENBERGHE DOI101093/BRAIN/AWW057 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Post-mortem Braak staging of neurofibrillary tau tangle topographical distribution is one of the core neuropathological criteria for the diagnosis of Alzheimers disease. The recent development of positron emission tomography tracers targeting neurofibrillary tangles has enabled the distribution of tau pathology to be imaged in living subjects. Methods for extraction of classic Braak staging from in vivo imaging of neurofibrillary tau tangles have not yet been explored. Standardized uptake value ratio images were calculated from 80-100 minute (18)F-AV-1451 (also known as T807) positron emission tomography scans obtained from n = 14 young reference subjects (age 21-39 years, Mini-Mental State Examination 29-30) and n = 173 older test subjects (age 50-95 years) comprising amyloid negative cognitively normal (n = 42), clinically-diagnosed mild cognitive impairment (amyloid positive, n = 47, and amyloid negative, n = 40) and Alzheimers disease (amyloid positive, n = 28, and amyloid negative, n = 16). We defined seven regions of interest in anterior temporal lobe and occipital lobe sections corresponding closely to those used as decision points in Braak staging. An algorithm based on the Braak histological staging procedure was applied to estimate Braak stages directly from the region of interest profiles in each subject. Quantitative region-based analysis of (18)F-AV-1451 images yielded region of interest and voxel level profiles that mirrored key features of neuropathological tau progression including profiles consistent with Braak stages 0 through VI. A simple set of decision rules enabled plausible Braak stages corresponding to stereotypical progression patterns to be objectively estimated in 149 (86%) of test subjects. An additional 12 (7%) subjects presented with predefined variant profiles (relative sparing of the hippocampus and/or occipital lobe). The estimated Braak stage was significantly associated with amyloid status, diagnostic category and measures of global cognition. In vivo (18)F-AV-1451 positron emission tomography images across the Alzheimers disease spectrum could be classified into patterns similar to those prescribed by Braak neuropathological staging of tau pathology.

Cerebrovascular hemodynamics in arteriovenous malformation complicated by normal perfusion pressure breakthrough

Catastrophic hyperemic states are known complications after the treatment of certain types of intracranial arteriovenous malformations (AVMs). A case is presented in which a large AVM was preoperatively embolized and later resected. There was clear intra- and postoperative evidence of edema and hemorrhage, which resulted in a fatal outcome. Regional cerebral blood flow (rCBF) data from this patient obtained with single photon emission computed tomography (SPECT) both before and after embolization were compared with data from four patients with similar size supratentorial AVMs treated and studied in a similar protocol who did not develop perfusion breakthrough. Pretreatment hemispheric rCBF was significantly reduced in this patients ipsilateral hemisphere (50 ml/100 g/min) compared to the control group mean (83 +/- 9.5 ml/100 g/min). A similar relative depression was found in the contralateral hemisphere. After therapeutic embolization, the ipsilateral rCBF increased by 33 ml/100 g/min and the contralateral hemispheric rCBF increased by 30 ml/100 g/min; this embolization-induced increase in rCBF was significantly higher than in the control group. Acetazolamide, known to increase rCBF in normal tissue by 35 +/- 3%, resulted in a 56% augmentation of ipsilateral hemispheric flow before embolization in the reported patient vs. a 22 +/- 10% increase for the control group. Postembolization, this hyperresponsiveness to acetazolamide remained unchanged. It is possible that these hemodynamic derangements may indicate a dissociation between the vasoconstrictive and vasodilatory reactivity in chronically hypoperfused territories adjacent to AVMs such that pharmacological or metabolic stimuli may induce further vasodilation, but sudden redistribution of large volumes of flow will not promote protective vasoconstriction.

Risk Factors for β-Amyloid Deposition in Healthy Aging: Vascular and Genetic Effects

IMPORTANCE Identifying risk factors for increased β-amyloid (Aβ) deposition is important for targeting individuals most at risk for developing Alzheimer disease and informing clinical practice concerning prevention and early detection. OBJECTIVE To investigate risk factors for Aβ deposition in cognitively healthy middle-aged and older adults. Specifically, we hypothesized that individuals with a vascular risk factor such as hypertension, in combination with a genetic risk factor for Alzheimer disease (apolipoprotein E ε4 allele), would show greater amyloid burden than those without such risk. DESIGN Cross-sectional study. SETTING General community. PARTICIPANTS One hundred eighteen well-screened and cognitively normal adults, aged 47 to 89 years. Participants were classified in the hypertension group if they reported a medical diagnosis of hypertension or if blood pressure exceeded 140 mm Hg systolic/90 mm Hg diastolic, as measured across 7 occasions at the time of study. INTERVENTION Participants underwent Aβ positron emission tomography imaging with radiotracer fluorine 18-labeled florbetapir. Participants were genotyped for apolipoprotein E and were classified as ε4(+) or ε4(-). MAIN OUTCOME MEASURE Amyloid burden. RESULTS Participants in the hypertension group with at least 1 ε4 allele showed significantly greater amyloid burden than those with only 1 risk factor or no risk factors. Furthermore, increased pulse pressure was strongly associated with increased mean cortical amyloid level for subjects with at least 1 ε4 allele. CONCLUSIONS AND RELEVANCE Vascular disease is a prevalent age-related condition that is highly responsive to both behavioral modification and medical treatment. Proper control and prevention of risk factors such as hypertension earlier in the life span may be one potential mechanism to ameliorate or delay neuropathological brain changes with aging.

The Centiloid Project: Standardizing quantitative amyloid plaque estimation by PET

Although amyloid imaging with PiB‐PET ([C‐11]Pittsburgh Compound‐B positron emission tomography), and now with F‐18‐labeled tracers, has produced remarkably consistent qualitative findings across a large number of centers, there has been considerable variability in the exact numbers reported as quantitative outcome measures of tracer retention. In some cases this is as trivial as the choice of units, in some cases it is scanner dependent, and of course, different tracers yield different numbers. Our working group was formed to standardize quantitative amyloid imaging measures by scaling the outcome of each particular analysis method or tracer to a 0 to 100 scale, anchored by young controls (≤45 years) and typical Alzheimers disease patients. The units of this scale have been named “Centiloids.” Basically, we describe a “standard” method of analyzing PiB PET data and then a method for scaling any “nonstandard” method of PiB PET analysis (or any other tracer) to the Centiloid scale.