ACR-ASNR Practice Parameter for Brain PET/CT Imaging Dementia.

This practice parameter is for both FDG and amyloid brain PET or PET/computed tomography (CT) for patients with cognitive decline, and has been developed collaboratively by the American College of Radiology (ACR) and the American Society for Neuroradiology (ASNR). It is estimated that the number of people with dementia, 36.5 million worldwide in 2010, will increase to 65.7 million in 2030 and to 115 million in 2050. Four primary neurodegenerative etiologies of dementia have been defined: Alzheimer disease (AD), vascular dementia, frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Alzheimer disease is the most common form of dementia, accounting for approximately 60%-80% of all cases. Indications for FDG and amyloid brain PET and qualifications for personnel are discussed in this practice parameter.

Interventional Magnetic Resonance Imaging Clinic: The Emory University Experience.

In this article, we share our experience in establishing a clinic-based practice for MR imaging-guided interventions. Clinic resources and operational logistics are described and our institutional cost analysis for supporting the clinic activity is provided. We highlight the overall value of the clinic model in transitioning the field of interventional MR imaging from the "proof-of-concept" to the "working model" era and engage in a detailed discussion of our experience with the positive impact of the clinic on streamlining the procedural workflow, increasing awareness of the technology, expanding referral bases, and boosting the satisfaction of both patients and referring services.

The role of imaging in United States courtrooms.

The rapid evolution of brain imaging techniques has increasingly offered more detailed diagnostic and prognostic information about neurologic and psychiatric disorders and the structural and functional brain changes that may influence behavior. Coupled with these developments is the increasing use of neuroimages in courtrooms, where they are used as evidence in criminal cases to challenge a defendant's competency or culpability and in civil cases to establish physical injury or toxic exposure. Several controversies exist, including the admissibility of neuroimages in legal proceedings, the reliability of expert testimony, and the appropriateness of drawing conclusions in individual cases based on the findings of research uses of imaging technology. This article reviews and discusses the current state of these issues.

Measurement of 5-HT1A receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [11C]WAY-100635.

OBJECTIVE: To assess effects of chronic antidepressant drug treatment on serotonin type-1A receptor (5-HT(1A)R) binding potential (BP) in major depressive disorder. METHODS: Depressed subjects (n = 27) were imaged using PET and [(11)C]WAY-100635 at baseline and following a median of 9.4 weeks of treatment with selective serotonin reuptake inhibitor or dual reuptake inhibitor antidepressant agents. Fifteen subjects had complete pre- and post-treatment scan data. The 5-HT(1A)R BP was derived from the tissue time-radioactivity concentrations from regions-of-interest defined a priori, using a simplified reference tissue model (SRTM), and in a subset of subjects, compartmental modeling (CMOD). RESULTS: Chronic treatment had no effect on pre- or post-synaptic 5-HT(1A)R BP, as confirmed by both the SRTM and CMOD analyses. These results were unaffected by treatment response status and were consistent across brain regions. Among the 22 subjects for whom the clinical response-to-treatment was established, the treatment nonresponders (n = 7) had higher baseline BP values in the left (P = 0.01) and right orbital cortex (P = 0.02) than the responders (n = 15). CONCLUSIONS: Chronic antidepressant drug treatment did not significantly change cerebral 5-HT(1A)R binding, consistent with preclinical evidence that the alterations in serotonergic function associated with antidepressant drug administration are not accompanied by changes in 5-HT(1A)R density. Higher baseline 5-HT(1A)R binding was associated with poorer response to treatment.

Ventricular volume and dementia progression in the Cardiovascular Health Study.

Elevated cerebral ventricular volume may be associated with dementia risk and progression. A fully-automated technique that agreed highly with radiological readings was used to estimate lateral ventricle volume on MR scans done at baseline in 1997-99 of 377 subjects in the Cardiovascular Health Study (CHS) from the Pittsburgh Center. 327 subjects were normal or diagnosed with mild cognitive impairment (MCI) at baseline and were evaluated 4 years later. Baseline ventricular volume was analyzed in multivariate models with age, gender, education level, presence and incidence of cerebral infarcts, and dementia category (normal, MCI, or dementia) at baseline and follow-up as fixed effects. Ventricular volume at baseline was significantly higher among subjects normal at baseline and demented 4 years later. Age, gender, education level, and dementia progression were significant factors affecting ventricular volume. Ventricular volume was higher in dementia compared to MCI, higher in MCI compared to controls, and higher in Possible-Alzheimer's-disease (AD) dementia compared to Probable-AD. Larger ventricles in healthy subjects may indicate susceptibility to, or progression of, dementia-related pathology.

Three-dimensional patterns of hippocampal atrophy in mild cognitive impairment.

OBJECTIVE: To measure hippocampal volumes in patients diagnosed as having subtypes of mild cognitive impairment (MCI) relative to those of elderly control subjects and those of patients with Alzheimer disease (AD) using 3-dimensional mesh reconstructions. DESIGN: A magnetic resonance imaging volumetric study of MCI subgroups (MCI, amnesic subtype [MCI-A]; and MCI, multiple cognitive domain subtype) using 3-dimensional mesh reconstructions of the structure. SETTING: Referral dementia clinic. SUBJECTS: Twenty-six subjects with MCI (MCI-A, n = 6; and MCI, multiple cognitive domain subtype, n = 20), 20 subjects with AD, and 20 controls who were equivalent in age, education, and sex distributions. MAIN OUTCOME MEASURES: Three-dimensional parametric mesh models of the hippocampus and total hippocampal volumes. RESULTS: The hippocampi of the patients with AD were significantly atrophic relative to those of the healthy controls. The MCI, multiple cognitive domain subtype, group did not differ from the controls, yet was significantly different from the MCI-A and the AD groups. The MCI-A patients had significant hippocampal atrophy compared with the controls, and did not differ significantly from the patients with AD. CONCLUSION: These data add to the growing evidence that there are multiple forms of MCI, that they have distinct neuropathological correlates, and that MCI, multiple cognitive domain subtype, is not a more advanced form of the MCI-A subtype.

Differential cortical atrophy in subgroups of mild cognitive impairment.

OBJECTIVE: To compare gray matter brain volumes in patients diagnosed with subtypes of mild cognitive impairment (MCI) (those with a focal amnestic disorder and those with more diffuse cognitive dysfunction) with those of elderly controls. DESIGN: Magnetic resonance imaging volumetric study of MCI subgroups (MCI-amnestic [MCI-A], and MCI-multiple cognitive domain [MCI-MCD]) using a whole brain voxel-based analysis. SETTING: Referral dementia clinic. Patients Thirty-seven patients with MCI (age range, 49-85 years; MCI-A, n = 9; MCI-MCD, n = 28) and 47 control subjects (age range, 55-81 years). MAIN OUTCOME MEASURES: Volumetric anatomical magnetic resonance imaging differences between MCI subgroups and normal controls, and between patients with MCI who progressed to dementia. Magnetic resonance imaging scans were analyzed using statistical software SPM99. RESULTS: Overall, the patients with MCI had significantly decreased volume in the hippocampus and middle temporal gyrus, bilaterally, compared with control subjects. Compared with patients with MCI-MCD, patients with MCI-A had significant volume loss of the left entorhinal cortex and inferior parietal lobe. Compared with patients with MCI-A, patients with MCI-MCD had significantly reduced volume of the right inferior frontal gyrus, right middle temporal gyrus, and bilateral superior temporal gyrus. Patients with MCI who progressed to Alzheimer disease during follow-up (mean interval 2 years, maximum 4.5 years), showed greater atrophy in the left entorhinal cortex, bilateral superior temporal gyri, and right inferior frontal gyrus compared with those who did not progress. CONCLUSIONS: These data provide evidence of distinct brain structural abnormalities in 2 groups of patients with MCI. While both have mesial temporal and cortical volume loss, those with a focal memory deficit have more involvement of the mesial temporal structures and less involvement of the neocortical heteromodal association areas than those patients with MCI with diffuse cognitive dysfunction. Thus, MCI may represent a more heterogeneous group than currently conceived, possibly reflecting 2 different etiological processes to dementia. These data also suggest that these structural abnormalities precede the development of Alzheimer disease.

Atlas-based hippocampus segmentation in Alzheimer's disease and mild cognitive impairment.

This study assesses the performance of public-domain automated methodologies for MRI-based segmentation of the hippocampus in elderly subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Structural MR images of 54 age- and gender-matched healthy elderly individuals, subjects with probable AD, and subjects with MCI were collected at the University of Pittsburgh Alzheimer's Disease Research Center. Hippocampi in subject images were automatically segmented by using AIR, SPM, FLIRT, and the fully deformable method of Chen to align the images to the Harvard atlas, MNI atlas, and randomly selected, manually labeled subject images ("cohort atlases"). Mixed-effects statistical models analyzed the effects of side of the brain, disease state, registration method, choice of atlas, and manual tracing protocol on the spatial overlap between automated segmentations and expert manual segmentations. Registration methods that produced higher degrees of geometric deformation produced automated segmentations with higher agreement with manual segmentations. Side of the brain, presence of AD, choice of reference image, and manual tracing protocol were also significant factors contributing to automated segmentation performance. Fully automated techniques can be competitive with human raters on this difficult segmentation task, but a rigorous statistical analysis shows that a variety of methodological factors must be carefully considered to insure that automated methods perform well in practice. The use of fully deformable registration methods, cohort atlases, and user-defined manual tracings are recommended for highest performance in fully automated hippocampus segmentation.

Gender differences in a fenfluramine-activated FDG PET study of borderline personality disorder.

Neuroimaging studies of impulsive-aggressive subjects with borderline personality disorder (BPD) demonstrate hypometabolism in areas of prefrontal and frontal cortex, and a blunted cortical metabolic response to challenge with serotonergic agonists. Neuroendocrine responses to serotonergic challenge are known to vary greatly by gender, and may be related to sex differences in expression of impulsive aggression. We conducted single-blind, placebo-controlled fenfluramine-activated positron emission tomography (PET) studies in impulsive male and female subjects with BPD to look for gender differences in cortical response. The sample comprised 22 BPD (15 female, 7 male) and 24 control subjects (10 female, 14 male) who received placebo on Day 1 and d,l-fenfluramine on Day 2 before PET neuroimaging. In response to placebo, female, but not male, controls had areas of increased uptake of fluorodeoxyglucose-F18 in prefrontal cortex compared with BPD subjects, with greatest uptake in the medial orbital frontal cortex, bilaterally. Male, but not female, BPD subjects, showed areas of increased glucose utilization compared with controls in large areas of parietal and occipital cortex, bilaterally. In response to fenfluramine (relative to placebo), significant decreases in glucose uptake were found in male, but not female, BPD subjects, centered in the left temporal lobe. Female, but not male, control subjects showed significantly decreased uptake in areas of right frontal and temporal cortex. Covarying for impulsive-aggression rendered nonsignificant the gender differences in responses to placebo or fenfluramine. Gender differences in serotonergic function may mediate differences in behavioral expression of impulsive aggression in subjects with BPD.

Serotonin 1A receptor binding and treatment response in late-life depression.

Depression in late life carries an increased risk of dementia and brittle response to treatment. There is growing evidence to support a key role of the serotonin type 1A (5-HT(1A)) receptor as a regulator of treatment response, particularly the 5-HT(1A) autoreceptor in the dorsal raphe nucleus (DRN). We used [11C]WAY 100635 and positron emission tomography (PET) to test our hypothesis that 5-HT(1A) receptor binding in the DRN and prefrontal cortex is altered in elderly depressives and that these measures relate to treatment responsivity. We studied 17 elderly subjects with untreated (nonpsychotic, nonbipolar) major depression (four men, 13 women; mean age: 71.4+/-5.9) and 17 healthy control subjects (eight men, nine women; mean age: 70.0+/-6.7). Patients were subsequently treated with paroxetine as part of a clinical trial of maintenance therapies in geriatric depression. [11C]WAY 100635 PET imaging was acquired and binding potential (BP) values derived using compartmental modeling. We observed significantly diminished [11C]WAY 100635 binding in the DRN in depressed (BP = 2.31+/-0.90) relative to control (BP = 3.69+/-1.56) subjects (p = 0.0016). Further, the DRN BP was correlated with pretreatment Hamilton Depression Rating Scores (r = 0.60, p = 0.014) in the depressed cohort. A trend level correlation between DRN binding and time to remission (r = 0.52, p = 0.067) was observed in the 14 depressed patients for whom these data were available. Our finding of decreased [11C]WAY 100635 binding in the brainstem region of the DRN in elderly depressed patients supports evidence of altered 5-HT(1A) autoreceptor function in depression. Further, this work indicates that dysfunction in autoreceptor activity may play a central role in the mechanisms underlying treatment response to selective serotonin reuptake inhibitors in late-life depression.

The nature and determinants of neuropsychological functioning in late-life depression.

CONTEXT: Cognitive impairment in late-life depression (LLD) is highly prevalent, disabling, poorly understood, and likely related to long-term outcome. OBJECTIVES: To determine the characteristics and determinants of neuropsychological functioning LLD. DESIGN: Cross-sectional study of groups of LLD patients and control subjects. SETTING: Outpatient, university-based depression research clinic. PARTICIPANTS: One hundred patients without dementia 60 years and older who met DSM-IV criteria for current episode of unipolar major depression (nonpsychotic) and 40 nondepressed, age- and education-equated control subjects. MAIN OUTCOME MEASURES: A comprehensive neuropsychological battery. RESULTS: Relative to control subjects, LLD patients performed poorer in all cognitive domains. More than half exhibited significant impairment (performance below the 10th percentile of the control group). Information processing speed and visuospatial and executive abilities were the most broadly and frequently impaired. The neuropsychological impairments were mediated almost entirely by slowed information processing (beta =.45-.80). Education (beta =.32) and ventricular atrophy (beta =.28) made additional modest contributions to variance in measures of language ability. Medical and vascular disease burden, apolipoprotein E genotype, and serum anticholinergicity did not contribute to variance in any cognitive domain. CONCLUSIONS: Late-life depression is characterized by slowed information processing, which affects all realms of cognition. This supports the concept that frontostriatal dysfunction plays a key role in LLD. The putative role of some risk factors was validated (eg, advanced age, low education, depression severity), whereas others were not (eg, medical burden, age at onset of first depressive episode). Further studies of neuropsychological functioning in remitted LLD patients are needed to parse episode-related and persistent factors and to relate them to underlying neural dysfunction.

Impulsivity and prefrontal hypometabolism in borderline personality disorder.

Prefrontal hypoperfusion and decreased glucose uptake in the prefrontal cortex (PFC) are found in violent criminal offenders, murderers and aggressive psychiatric patients. These abnormalities may be independent of diagnosis and associated with impulsive-aggression as a personality trait. Impulsive-aggression is a clinical characteristic of borderline personality disorder (BPD) where it is associated with assaultive and suicidal behaviors. We conducted FDG-PET studies in 13 non-depressed, impulsive female subjects with BPD and 9 healthy controls to look for abnormalities in glucose metabolism in areas of the PFC associated with regulation of impulsive behavior. Statistical Parametric Mapping-99 (SPM99) was used to analyze the PET data with Hamilton depression scores as covariate. Significant reductions in FDG uptake in BPD subjects relative to healthy controls were found bilaterally in medial orbital frontal cortex, including Brodmann's areas 9, 10 and 11. There were no significant areas of increased uptake in BPD subjects compared to control subjects. Covarying for measures of impulsivity or impulsive-aggression rendered insignificant the differences between groups. Decreased glucose uptake in medial orbital frontal cortex may be associated with diminished regulation of impulsive behavior in BPD.

PET/CT imaging in recurrent head and neck cancer.

PET/CT offers advantages over PET alone, which is limited by poor anatomic localization and CT alone, which provides morphologic data only. Retrospective fusion of separately acquired PET and CT images allows for potential fusion misregistration in the mobile head and neck between imaging sessions. Indications for PET/CT include recurrent neoplasm, tumor surveillance, and staging. This article will focus on recurrent head and neck neoplasm including, head and neck cancer, thyroid cancer, recurrent skull base tumor. PET/CT may change management in facilitating earlier detection of recurrence than is possible with conventional CT or MR imaging, in guiding biopsy, and in detecting second primary sites and distant metastases. Limitations of PET/CT include physiologic uptake, metabolically active tissue, and muscle contraction during uptake phase. PET/CT, however, is better equipped than is PET alone to mitigate these limitations by precisely localizing FDG uptake to anatomic structures. In addition, small lesions (< 1 cm) may be below scanner resolution and, therefore, a lower SUV (that is < or = 3), may suggest neoplasm. Recent treatment may result in false negative findings, especially when PET is performed within 4 months of radiation therapy. Finally, tumors of low metabolic activity (e.g., salivary gland tumors) may be prone to false negative results. In the future, PET/CT imaging will become more useful in staging head and neck cancer with improved scanner resolution. Development of specific tumor markers may allow for tumor-specific ligands that will increase sensitivity to head and neck neoplasia. Treatment targeting for radiation therapy is an application that is likely to become widely used.

Heterogeneity of microvascular dysfunction in women with chest pain not attributable to coronary artery disease: implications for clinical practice.

BACKGROUND: Women with chest pain in the absence of obstructive coronary artery disease (CAD) frequently have coronary microvascular dysfunction and inducible myocardial ischemia. Microvascular dysfunction is commonly diagnosed by demonstrating abnormal flow reserve in a single coronary artery during angiography. Therefore, diagnostic accuracy is dependent on homogeneity of microvascular dysfunction in the myocardium. METHODS: In the Women's Ischemia Syndrome Evaluation (WISE), 34 women with chest pain and no significant CAD and 9 female control subjects underwent 13N-NH3 positron emission tomography to measure adenosine-induced changes in myocardial perfusion (ie, coronary flow reserve [CFR]). Flow reserve was correlated among the left anterior descending (LAD), circumflex (LCx), and right (RCA) coronary artery distributions. RESULTS: The mean CFR in the LAD, LCx, and RCA was 2.85 +/- 1.35, 2.58 +/- 0.94, and 3.24 +/- 1.42, respectively. Concordance in the classification of microvascular function as normal (CFR > or =2.5) versus abnormal was present in the LAD and RCA, LAD and LCx, and RCA and LCx distributions in only 71.8%, 66.7%, and 61.6% of patients, respectively. There was a modest degree of correlation of CFR between the LAD and RCA (r = 0.79, P <.001), LAD and LCx (r = 0.61, P <.001), and LCx and RCA (r = 0.57, P <.001). Comparison of CFR in the 3 coronary arteries simultaneously in all patients demonstrated that the LCx had values that were significantly lower than the RCA and LAD distributions. CONCLUSION: Substantial discordance of classification of microvascular function among coronary artery distributions in women with chest pain and no CAD suggests that microvascular dysfunction is distributed heterogeneously in the myocardium. Assessment of CFR in a single coronary artery during cardiac catheterization may not provide an accurate assessment of the coronary microcirculation in women with chest pain not attributable to CAD.

Neuronal transplantation for motor stroke: from the laboratory to the clinic.

Laboratory studies have established the potential for neuronal transplantation to be of benefit to patients. Experimental studies in normal animals indicate that brain implantation of neurons seems safe. Implanted neurons integrated with the host brain, sent out axonal processes to communicate with other nerve cells, released transmitters (the chemical messengers of nerve cell communication), and demonstrated typical neuronal proteins. This article discusses phase I and II trials of neuronal transplantation in humans with small strokes in critical brain locations such as the basal ganglia region. More work is needed to confirm safety and to identify optimal measures of efficacy in this setting.

Positron emission tomography imaging of the aging brain.

PET imaging provides a vital means to study the human brain in vivo in aging and early disease states. PET studies using selective markers for brain metabolism and neurotransmitter function have uncovered a wealth of information on healthy and pathologic brain aging, and its relationship to behavior and mood states. Recognition of inherent potential confounds in the use of PET in aging studies is essential to the proper interpretation of these data.

MR atlas of the baboon brain for functional neuroimaging.

Mathematical co-registration of functional image data (e.g., positron emission tomography, PET) to anatomical magnetic resonance (MR) imaging data allows for objective associations between function and anatomy. Baboons are often used as non-human primate models for functional neuroimaging studies. In this work, a digital MR-based high-resolution atlas of the baboon brain was generated and evaluated for PET. The atlas was generated from six SPGR-MR datasets (centered at mid-sagittal line, AC-PC orientation) that were transformed into the space of one representative MR, averaged and resampled into PET space. The atlas was evaluated by comparing blood flow and dopamine receptor and serotonin transporter binding measures determined using regions-of-interest (ROIs) generated on each individual co-registered MR (ROI(i)) and the atlas-defined ROI template (ROI(ATLAS)). Common ROIs applied to all data included frontal cortex, temporal cortex, thalamus, caudate, putamen and cerebellum. High correlations (r(2)>0.87) were found between the ROI(i) and ROI(ATLAS) data for all radiotracers (linear regression across ROIs for each baboon). The average regression slope values ranged from 0.95 to 1.02 across radiotracers. Lastly, use of the atlas for statistical parametric mapping (SPM) of [15O]water data yielded good agreement with previous ROI(i) results. Overall, the digital MR-based atlas allowed for automatic co-registration, proved useful across a range of PET Studies, and is accessible electronically via the Internet.