Sensorimotor network segregation declines with age and is linked to GABA and to sensorimotor performance.

Aging is typically associated with declines in sensorimotor performance. Previous studies have linked some age-related behavioral declines to reductions in network segregation. For example, compared to young adults, older adults typically exhibit weaker functional connectivity within the same functional network but stronger functional connectivity between different networks. Based on previous animal studies, we hypothesized that such reductions of network segregation are linked to age-related reductions in the brain's major inhibitory transmitter, gamma aminobutyric acid (GABA). To investigate this hypothesis, we conducted graph theoretical analyses of resting state functional MRI data to measure sensorimotor network segregation in both young and old adults. We also used magnetic resonance spectroscopy to measure GABA levels in the sensorimotor cortex and collected a battery of sensorimotor behavioral measures. We report four main findings. First, relative to young adults, old adults exhibit both less segregated sensorimotor brain networks and reduced sensorimotor GABA levels. Second, less segregated networks are associated with lower GABA levels. Third, less segregated networks and lower GABA levels are associated with worse sensorimotor performance. Fourth, network segregation mediates the relationship between GABA and performance. These findings link age-related differences in network segregation to age-related differences in GABA levels and sensorimotor performance. More broadly, they suggest a neurochemical substrate of age-related dedifferentiation at the level of large-scale brain networks.

Michigan Neural Distinctiveness (MiND) study protocol: investigating the scope, causes, and consequences of age-related neural dedifferentiation.

BACKGROUND: Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway). METHODS: The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity. DISCUSSION: By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines. TRIAL REGISTRATION: This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136 .

Striatal and Cortical ß-Amyloidopathy and Cognition in Parkinson's Disease.

INTRODUCTION: Although most previous cognitive studies of ß-amyloidopathy in PD focused on cortical plaque deposition, recent postmortem studies point to an important role of striatal ß-amyloid plaque deposition. The aim of this study was to investigate the relative contributions of striatal and cortical ß-amyloidopathy to cognitive impairment in PD. METHODS: Patients with PD (n = 62; age, 68.9 ± 6.4 years; H & Y stage: 2.7 ± 0.5; MoCA score: 25.2 ± 3.0) underwent [(11) C]Pittsburgh compound B ß-amyloid, [(11) C]dihydrotetrabenazine monoaminergic, and [(11) C]methyl-4-piperidinyl propionate acetylcholinesterase brain PET imaging and neuropsychological assessment. [(11) C]Pittsburgh compound B ß-amyloid data from young to middle-aged healthy subjects were used to define elevated [(11) C]Pittsburgh compound B binding in patients. RESULTS: Elevated cortical and striatal ß-amyloid deposition were present in 37% and 16%, respectively, of this predominantly nondemented cohort of patients with PD. Increased striatal ß-amyloid deposition occurred in half of all subjects with increased cortical ß-amyloid deposition. In contrast, increased striatal ß-amyloid deposition did not occur in the absence of increased cortical ß-amyloid deposition. Analysis of covariance using global composite cognitive z scores as the outcome parameter showed significant regressor effects for combined striatal and cortical ß-amyloidopathy (F = 4.18; P = 0.02) after adjusting for covariate effects of cortical cholinergic activity (F = 5.67; P = 0.02), caudate nucleus monoaminergic binding, duration of disease, and age (total model: F = 3.55; P = 0.0048). Post-hoc analysis showed significantly lower cognitive z score for combined striatal and cortical ß-amyloidopathy, compared to cortical-only ß-amyloidopathy and non-ß-amyloidopathy subgroups. CONCLUSIONS: The combined presence of striatal and cortical ß-amyloidopathy is associated with greater cognitive impairment than cortical ß-amyloidopathy alone in PD.

Amyloid deposition in Parkinson's disease and cognitive impairment: a systematic review.

BACKGROUND: Varying degrees of cortical amyloid deposition are reported in the setting of Parkinsonism with cognitive impairment. We performed a systematic review to estimate the prevalence of Alzheimer disease (AD) range cortical amyloid deposition among patients with Parkinson's disease with dementia (PDD), Parkinson's disease with mild cognitive impairment (PD-MCI) and dementia with Lewy bodies (DLB). We included amyloid positron emission tomography (PET) imaging studies using Pittsburgh Compound B (PiB). METHODS: We searched the databases Ovid MEDLINE, PubMed, Embase, Scopus, and Web of Science for articles pertaining to amyloid imaging in Parkinsonism and impaired cognition. We identified 11 articles using PiB imaging to quantify cortical amyloid. We used the metan module in Stata, version 11.0, to calculate point prevalence estimates of patients with "PiB-positive" studies, that is, patients showing AD range cortical Aß-amyloid deposition. Heterogeneity was assessed. A scatterplot was used to assess publication bias. RESULTS: Overall pooled prevalence of "PiB-positive" studies across all three entities along the spectrum of Parkinson's disease and impaired cognition (specifically PDD, PD-MCI, and DLB) was 0.41 (95% confidence interval [CI], 0.24-0.57). Prevalence of "PiB-positive" studies was 0.68 (95% CI, 0.55-0.82) in the DLB group, 0.34 (95% CI, 0.13-0.56) in the PDD group, and 0.05 (95% CI, -0.07-0.17) in the PD-MCI group. CONCLUSIONS: Substantial variability occurs in the prevalence of "PiB-positive" studies in subjects with Parkinsonism and cognitive impairment. Higher prevalence of PiB-positive studies was encountered among subjects with DLB as opposed to subjects with PDD. The PD-MCI subjects showed overall lower prevalence of PiB-positive studies than reported findings in non-PD-related MCI. © 2015 International Parkinson and Movement Disorder Society.

ß-Amyloid and postural instability and gait difficulty in Parkinson's disease at risk for dementia.

Although motor impairments in Parkinson's disease (PD) are attributed to nigrostriatal dopaminergic denervation, postural instability and gait difficulty (PIGD) features are less responsive to dopaminergic medications. PIGD features are a risk factor also for the development of dementia in PD (PDD). These observations suggest that nondopaminergic mechanisms may contribute to axial motor impairments. The aim was to perform a correlative PET study to examine the relationship between neocortical ß-amyloid deposition ([(11)C]-Pittsburgh Compound B), nigrostriatal dopaminergic denervation ([(11)C]-dihydrotetrabenazine), and PIGD feature severity in PD patients at risk for dementia. This was a cross-sectional study of 44 PD patients (11 female and 33 male; 69.5 ± 6.6 years of age; 7.0 ± 4.8 years motor disease duration; mean H & Y stage: 2.7 ± 0.5) who underwent PET, motor feature severity assessment using the Movement Disorder Society revised UPDRS, and the Dementia Rating Scale (DRS). Linear regression (R(2)(adj) = 0.147; F(4,39) = 2.85; P = 0.036) showed that increased PIGD feature severity was associated with increased neocortical [(11)C]-Pittsburgh Compound B binding (ß = 0.346; t(39) = 2.13; P = 0.039) while controlling for striatal [(11)C]-dihydrotetrabenazine binding, age, and DRS total score. Increased neocortical ß-amyloid deposition, even at low-range levels, is associated with higher PIGD feature severity in PD patients at risk for dementia. This finding may explain why the PIGD motor phenotype is a risk factor for the development of PDD.

Pregabalin rectifies aberrant brain chemistry, connectivity, and functional response in chronic pain patients.

BACKGROUND: Chronic pain remains a significant challenge for modern health care as its pathologic mechanisms are largely unknown and preclinical animal models suffer from limitations in assessing this complex subjective experience. However, human brain neuroimaging techniques enable the assessment of functional and neurochemical alterations in patients experiencing chronic pain and how these factors may dynamically change with pharmacologic treatment. METHODS: To identify the clinical action of pregabalin, a proven analgesic, the authors performed three complementary brain neuroimaging procedures: (proton magnetic resonance spectroscopy, functional magnetic resonance imaging, and functional connectivity magnetic resonance imaging) in 17 chronic pain patients diagnosed with fibromyalgia. RESULTS: The authors found that pregabalin but not placebo reduces combined glutamate + glutamine levels within the posterior insula (pregabalin P = 0.016; placebo P = 0.71). Interestingly, reductions in clinical pain were associated with reductions in brain connectivity of this structure to brain regions within the default mode network during pregabalin (r = 0.82; P = 0.001) but not placebo (r = -0.13; P = 0.63). Response of default mode network regions to experimental pain was also reduced with pregabalin (P = 0.018) but not placebo (P = 0.182). Perhaps most importantly, baseline values for all three neuroimaging markers predicted subsequent analgesic response to pregabalin but not placebo. CONCLUSIONS: The results of this study suggest that pregabalin works in part by reducing insular glutamatergic activity, leading to a reduction of the increased functional connectivity seen between brain regions in chronic pain states. The study also supports a role for human brain imaging in the development, assessment, and personalized use of central-acting analgesics.

Reduced insular γ-aminobutyric acid in fibromyalgia.

OBJECTIVE: Recent scientific findings have reinvigorated interest in examining the role of γ-aminobutyric acid (GABA), the major inhibitory central nervous system neurotransmitter, in chronic pain conditions. Decreased inhibitory neurotransmission is a proposed mechanism in the pathophysiology of chronic pain syndromes such as fibromyalgia (FM). The purpose of this study was to test the hypothesis that decreased levels of insular and anterior cingulate GABA would be present in FM patients, and that the concentration of this neurotransmitter would be correlated with pressure-pain thresholds. METHODS: Sixteen FM patients and 17 age- and sex-matched healthy controls underwent pressure-pain testing and a 3T proton magnetic resonance spectroscopy session in which the right anterior insula, right posterior insula, anterior cingulate, and occipital cortex were examined in subjects at rest. RESULTS: GABA levels in the right anterior insula were significantly lower in FM patients compared with healthy controls (mean ± SD 1.17 ± 0.24 arbitrary institutional units versus 1.42 ± 0.32 arbitrary institutional units; P = 0.016). There was a trend toward increased GABA levels in the anterior cingulate of FM patients compared with healthy controls (P = 0.06). No significant differences between groups were detected in the posterior insula or occipital cortex (P > 0.05 for all comparisons). Within the right posterior insula, higher levels of GABA were positively correlated with pressure-pain thresholds in the FM patients (Spearman's rho = 0.63; P = 0.02). CONCLUSION: Diminished inhibitory neurotransmission resulting from lower concentrations of GABA within the right anterior insula may play a role in the pathophysiology of FM and other central pain syndromes.

Neuroimaging evaluation of non-accidental head trauma with correlation to clinical outcomes: a review of 57 cases.

OBJECTIVE: To review the clinical presentation and neuroimaging findings in patients with high clinical suspicion for non-accidental trauma (NAT) of the head, to investigate associations between imaging findings and long-term neurologic outcome in abused children. STUDY DESIGN: A retrospective review of 57 cases of NAT of the head from a single institution was performed. Neuroimaging studies (computed tomography [CT] and magnetic resonance imaging [MRI]) were reviewed by a senior neuroradiologist, a neuroradiology fellow, and a radiology resident. Clinical history and physical findings, including retinal examination, imaging, and follow-up assessment, were reviewed. RESULTS: The mean time between the patient's arrival at the hospital and CT and MRI imaging was 2.9 hours and 40.6 hours, respectively. The most common clinical presentation was mental status changes, seen in 47% of patients. The most common neuroimaging finding was subdural hematoma, seen in 86% of patients. In the 47 patients who underwent both MRI and CT, 1 case of suspected NAT was missed on head CT. CT detected signs of global ischemia in all 11 patients who died (mean time after arrival at the hospital until undergoing CT, 1.1 hours). MRI detected additional signs of injury in patients who developed mild to moderate developmental delay. CONCLUSION: CT was able to detect evidence of NAT of the head in 56 of 57 abused children included in our cohort and predicted severe neurologic injury and mortality. MRI was useful in detecting additional evidence of trauma, which can be helpful in risk stratification for neurologic outcomes as well in providing confirming evidence of repeated injury.

Sensitivity of orbital magnetic resonance imaging in acute demyelinating optic neuritis.

OBJECTIVE: To determine the sensitivity of orbital magnetic resonance imaging (MRI) in acute demyelinating optic neuritis (ON) in routine clinical practice, and the added value of a dedicated neuroradiology interpretation. DESIGN: Retrospective chart review. PARTICIPANTS: Patients with clinically proven ON evaluated between 2004 and 2014 in the University of Michigan neuro-ophthalmology clinics. Inclusion criteria involved visual recovery and orbital MRI completed within 30days of symptom onset and before corticosteroid treatment. METHODS: Demographics, clinical examination, and MRI report data (high T2 signal, gadolinium contrast enhancement) were abstracted for each eligible eye. Every MRI was reinterpreted by a neuroradiologist masked to the affected side. Descriptive statistics summarized patient and eye characteristics. Interrater agreement between the neuroradiologist and the radiology report for the radiographic diagnosis of ON was assessed with Cohen's kappa statistic. RESULTS: Of 92 patients who met all inclusion criteria, 70 (76.1%) were reported to have at least 1 MRI feature consistent with ON. After dedicated review by a neuroradiologist, 77 (83.7%) were determined to have a positive MRI for ON. Agreement between the neuroradiologist and MRI report was moderate (κ = 0.63). Gadolinium enhancement was the most common feature in MRI positive ON (72 [78.3%] of neuroradiology reviewed MRIs; 66 [71.7%] of clinical MRI reports). CONCLUSIONS: The sensitivity of MRI in ON was lower than previously reported and confirms the importance of making a clinical diagnosis of ON without relying on neuroimaging for confirmation. MRI interpretation by a skilled neuroradiologist increased sensitivity, underscoring the complexity of orbital MRI interpretation.

Age-Related Declines in Occipital GABA are Associated with Reduced Fluid Processing Ability.

RATIONALE AND OBJECTIVES: Healthy aging is associated with pervasive declines in cognitive, motor, and sensory functioning. There are, however, substantial individual differences in behavioral performance among older adults. Several lines of animal research link age-related reductions of gamma-aminobutyric acid (GABA), the brain's primary inhibitory neurotransmitter, to age-related cognitive, motor, and sensory decline. Our study used proton magnetic resonance spectroscopy (MRS) at 3T to explore whether occipital GABA declines with age in humans and whether individual differences in occipital GABA are linked to individual differences in fluid processing ability. MATERIALS AND METHODS: We used a MEGA-PRESS sequence that combines frequency spectral editing with a point-resolved spectroscopy sequence to quantify GABA. Spectra were obtained from a 30 × 30 × 25 mm voxel placed in the occipital cortex of 20 young adults (mean age 20.7 years) and 18 older adults (mean age 76.5 years). Participants also performed 11 fluid processing tasks outside the scanner, the results of which were z-scored and averaged to calculate a summary measure of fluid processing ability. Regression analysis was employed to determine the relationship between GABA concentrations in the occipital cortex and a summary measure of fluid processing ability. RESULTS: Occipital GABA was significantly lower in older participants compared to the younger participants. We also observed a significant positive relationship between occipital GABA and fluid processing ability. In fact, higher GABA was associated with better task performance in 10 of the 11 tasks. CONCLUSION: These findings suggest that GABA levels decline with age in humans and are associated with declines in fluid processing ability.

Building Imaging Institutes of Patient Care Outcomes: Imaging as a Nidus for Innovation in Clinical Care, Research, and Education.

Traditionally, radiologists have been responsible for the protocol of imaging studies, imaging acquisition, supervision of imaging technologists, and interpretation and reporting of imaging findings. In this article, we outline how radiology needs to change and adapt to a role of providing value-based, integrated health-care delivery. We believe that the way to best serve our specialty and our patients is to undertake a fundamental paradigm shift in how we practice. We describe the need for imaging institutes centered on disease entities (eg, lung cancer, multiple sclerosis) to not only optimize clinical care and patient outcomes, but also spur the development of a new educational focus, which will increase opportunities for medical trainees and other health professionals. These institutes will also serve as unique environments for testing and implementing new technologies and for generating new ideas for research and health-care delivery. We propose that the imaging institutes focus on how imaging practices-including new innovations-improve patient care outcomes within a specific disease framework. These institutes will allow our specialty to lead patient care, provide the necessary infrastructure for state-of-the art-education of trainees, and stimulate innovative and clinically relevant research.

How to Perform a Systematic Review and Meta-analysis of Diagnostic Imaging Studies.

A systematic review is a comprehensive search, critical evaluation, and synthesis of all the relevant studies on a specific (clinical) topic that can be applied to the evaluation of diagnostic and screening imaging studies. It can be a qualitative or a quantitative (meta-analysis) review of available literature. A meta-analysis uses statistical methods to combine and summarize the results of several studies. In this review, a 12-step approach to performing a systematic review (and meta-analysis) is outlined under the four domains: (1) Problem Formulation and Data Acquisition, (2) Quality Appraisal of Eligible Studies, (3) Statistical Analysis of Quantitative Data, and (4) Clinical Interpretation of the Evidence. This review is specifically geared toward the performance of a systematic review and meta-analysis of diagnostic test accuracy (imaging) studies.

Pulmonary nodule volumetric measurement variability as a function of CT slice thickness and nodule morphology.

OBJECTIVE: The purpose of our study was to assess differences in volumetric measurements of pulmonary nodules obtained using different CT slice thicknesses; correlate these differences with nodule size, shape, and margination; and compare measurements generated by two different software packages. MATERIALS AND METHODS: Seventy-five individual nodules identified on 29 lowdose, unenhanced, MDCT chest examinations were selected for volumetric analysis. Each image data set was reconstructed in three ways (slice thickness/reconstruction interval): 1.25 mm/0.625 mm, 2.5 mm/2 mm, and 5 mm/2.5 mm. Volumetric measurements were made on all 75 nodules at 1.25- and 2.5-mm slice thicknesses and on 57 of 75 nodules at the 5-mm thickness using Volume Analysis software. For 69 of 75 nodules, measurements were obtained on 1.25- and 2.5-mm-thick sections using a different commercially available software system, LN500 R2 software. Volume variability between different slice thicknesses was correlated with nodule diameter, shape, and margination using multiple linear regression. Percent differences between measurements obtained with the two software systems were calculated. Significance of relative volume differences between slice thicknesses and software packages was assessed using a one-sample Student's t-test. RESULTS: Although statistically significant differences in volumes between different section thicknesses were seen only for the tiny nodule size group, many individual nodules showed substantial volume variation. Significant differences were seen in nodule volume variability for smaller nodules (3-10 mm) compared with larger nodules (> or = 11 mm) (p < 0.0001), as well as spiculated compared with smooth nodules, within a single size group (p < 0.05). No effect of nodule shape (round vs elongated) was noted. Statistically significant differences in measurements obtained with the two software systems were seen only with 2.5-mm-thick sections (p = 0.001). CONCLUSION: CT slice thickness variation resulted in significant differences in volume measurements for tiny nodules. A spiculated margin was shown to have a significant effect on nodule volume variability within a single size group. Use of different software packages resulted in significant volume measurement differences at the 2.5-mm CT slice thickness.

Added utility of gadolinium in the magnetic resonance imaging (MRI) workup of seizures in children younger than 2 years.

The purpose of this study was to evaluate the added utility of gadolinium administration in the magnetic resonance imaging (MRI) workup of seizures in children younger than 2 years. A computerized retrospective search of the radiology information system identified all brain MRI examinations performed at the authors' institution from 1995 to 2002 for children younger than 2 years. Review of the clinical records revealed that 437 of a total 1466 brain magnetic resonance examinations performed on this subset of the pediatric population were performed as part of an initial seizure workup. Magnetic resonance reports and clinical notes were reviewed. MRI studies with enhancing lesions as well as those with equivocal findings were also reviewed in a consensus fashion by 2 senior neuro-radiologists and 2 radiology residents. Contrast administration was rated as essential, helpful, or not helpful for each study. Administration of contrast medium was felt to be essential in formulating a diagnosis in a total of 8 (1.8%) studies, all of which involved documented or highly suspected cases of infection. In an additional 26 cases (5.9%), which included 4 cases of neoplasm, contrast was felt to be useful but not essential in reaching a diagnosis. Contrast was judged not helpful in making the diagnosis in the other 403 studies (92.3%).

Manually adjusted versus vendor-preset definition of metabolite boundaries impact on proton metabolite ratios.

RATIONALE AND OBJECTIVES: Metabolite peak boundary definition is an important postprocessing step in proton magnetic resonance spectroscopy (1H-MRS). We compare metabolite ratios calculated using three different postprocessing strategies: software-rendered default peak boundaries, manually adjusted peak boundaries and a curve-fitting program. The first two of these methods are commercially available. MATERIALS AND METHODS: A total of 42 spectra acquired on a 1.5-T MR unit using two-dimensional chemical shift proton MR spectroscopy (TR/TE = 1500/144 ms) were analyzed. Choline (Cho), creatine (Cr), and N-acetylaspartate (NAA) relative concentrations were derived and the following metabolite ratios were calculated: Cho/Cr, Cho/NAA, and NAA/Cr. Metabolite concentrations/ratios were calculated using (a) default peak boundaries rendered by commercially available, postprocessing software (Functool 2000, version 2.6.0); (b) manually adjusted peak boundaries by an experienced spectroscopist, using an option offered by the same commercially available software; and (c) an offline in-house curve-fitting program. Measurements obtained with method (c) were considered as the "gold standard." Paired t-tests comparing default and adjusted metabolite ratios, as well as default and adjusted ratios with their respective curve-fit values were used for statistical analysis. RESULTS: Significant differences between default and manually adjusted values were found for Cho/Cr ratios <1.5 and for all Cho/NAA ratios. For Cho/Cr ratios <1.5, significant differences between default and curve-fit values were present; this was not the case when comparing manually adjusted and curve-fit values. Default and manually adjusted Cho/NAA ratios were significantly higher than corresponding curve-fit ratios. Manually adjusted values were, however, closer to the curve-fit values. No significant differences were noted between default and adjusted NAA/Cr values; default and manually adjusted ratios were significantly lower than curve-fit ratios. CONCLUSION: There can be significant differences in metabolite ratios calculated using default and manually adjusted peak limits in proton MR spectroscopy. Furthermore, Cho/Cr and NAA/Cho adjusted metabolite ratios are closer to curve-fit values, which are considered the most accurate of the three.

A Simplified Approach to Encephalitis and Its Mimics: Key Clinical Decision Points in the Setting of Specific Imaging Abnormalities.

RATIONALE AND OBJECTIVES: Infectious encephalitis is a relatively common cause of morbidity and mortality. Treatment of infectious encephalitis with antiviral medication can be highly effective when administered promptly. Clinical mimics of encephalitis arise from a broad range of pathologic processes, including toxic, metabolic, neoplastic, autoimmune, and cardiovascular etiologies. These mimics need to be rapidly differentiated from infectious encephalitis to appropriately manage the correct etiology; however, the many overlapping signs of these various entities present a challenge to accurate diagnosis. A systematic approach that considers both the clinical manifestations and the imaging findings of infectious encephalitis and its mimics can contribute to more accurate and timely diagnosis. MATERIALS AND METHODS: Following an institutional review board approval, a health insurance portability and accountability act (HIPAA)-compliant search of our institutional imaging database (teaching files) was conducted to generate a list of adult and pediatric patients who presented between January 1, 1995 and October 10, 2013 for imaging to evaluate possible cases of encephalitis. Pertinent medical records, including clinical notes as well as surgical and pathology reports, were reviewed and correlated with imaging findings. Clinical and imaging findings were combined to generate useful flowcharts designed to assist in distinguishing infectious encephalitis from its mimics. Key imaging features were reviewed and were placed in the context of the provided flowcharts. RESULTS: Four flowcharts were presented based on the primary anatomic site of imaging abnormality: group 1: temporal lobe; group 2: cerebral cortex; group 3: deep gray matter; and group 4: white matter. An approach that combines features on clinical presentation was then detailed. Imaging examples were used to demonstrate similarities and key differences. CONCLUSIONS: Early recognition of infectious encephalitis is critical, but can be quite complex due to diverse pathologies and overlapping features. Synthesis of both the clinical and imaging features of infectious encephalitis and its mimics is critical to a timely and accurate diagnosis. The use of the flowcharts presented in this article can further enable both clinicians and radiologists to more confidently differentiate encephalitis from its mimics and improve patient care.

Differentiation of recurrent brain tumor versus radiation injury using diffusion tensor imaging in patients with new contrast-enhancing lesions.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the use of diffusion tensor imaging (DTI) in the evaluation of new contrast-enhancing lesions and perilesional edema in patients previously treated for brain neoplasm in the differentiation of recurrent neoplasm from treatment-related injury. METHODS: Twenty-eight patients with new contrast-enhancing lesions and perilesional edema at the site of previously treated brain neoplasms were retrospectively reviewed. Nine directional echoplanar DTIs with b=1000 s/mm(2) were obtained using a single-shot spin-echo echoplanar imaging. Standardized regions of interest were manually drawn in several regions. Mean apparent diffusion coefficient (ADC), fractional anisotropy (FA) and eigenvalue indices (lambda( parallel) and lambda( perpendicular)) and their ratios relative to the contralateral side were compared in patients with recurrent neoplasm versus patients with radiation injury, as established by histological examination or by clinical course, including long-term imaging studies and magnetic resonance spectroscopy. RESULTS: The ADC values in the contrast-enhancing lesions were significantly higher (P=.01) for the recurrence group (range=1.01 x 10(-3) to 1.66 x 10(-3) mm(2)/s; mean+/-S.D.=1.27+/-0.15) than for the nonrecurrence group (range=0.9 x 10(-3) to 1.31 x 10(-3) mm(2)/s; mean+/-S.D.=1.12+/-0.14). The ADC ratios in the white matter tracts in perilesional edema trended higher (P=.09) in treatment-related injury than in recurrent neoplasm (mean+/-S.D.=1.85+/-0.30 vs. 1.60+/-0.27, respectively). FA ratios were significantly higher in normal-appearing white matter (NAWM) tracts adjacent to the edema in the nonrecurrence group (mean+/-S.D.=0.89+/-0.15) than in those in the recurrence group (mean+/-S.D.=0.74+/-0.14; P=.03). Both eigenvalue indices lambda( parallel) and lambda( perpendicular) were significantly higher in contrast-enhancing lesions in the recurrence group than in those in the nonrecurrence group (P=.02). As well, both eigenvalue indices lambda( parallel) and lambda( perpendicular) were significantly higher in perilesional edema than in normal white matter (P<.01 and P<.001, respectively) in both groups. CONCLUSION: The assessment of diffusion properties, especially ADC values and ADC ratios, in contrast-enhancing lesions, perilesional edema and NAWM adjacent to the edema in the follow-up of new contrast-enhancing lesions at the site of previously treated brain neoplasms may add to the information obtained by other imaging techniques in the differentiation of radiation injury from tumor recurrence.

Value of gadolinium in brain MRI examinations for developmental delay.

The aim of this study was to evaluate the added utility of gadolinium administration in the magnetic resonance imaging evaluation of developmental delay in children less than 2 years of age. A computerized retrospective study identified all brain magnetic resonance imaging examinations using gadolinium performed at our institution from 1995-2002 for children under the age of 2 years. Review of the clinical records and magnetic resonance imaging reports identified 170 brain magnetic resonance imaging examinations that were performed for developmental delay. Magnetic resonance imaging studies with enhancing lesions were reviewed by two staff neuroradiologists and two radiology residents. Contrast administration was rated as essential, helpful, or not helpful for each study. In the 107 patients in whom developmental delay was the primary concern, there were no cases in which the findings would have been missed without gadolinium administration. In the 63 patients in whom developmental delay was a secondary concern, there were several cases (11%) where contrast was helpful but not essential in reaching a radiologic diagnosis. In conclusion, intravenous gadolinium has an extremely low yield in children under the age of 2 where developmental delay is the primary concern. In young children for whom developmental delay is a secondary concern, we advocate the use of gadolinium particularly where tumor or infection is clinically suspected.

Imaging Amyloidopathy in Parkinson Disease and Parkinsonian Dementia Syndromes.

Dementia arising in patients with Parkinson disease or parkinsonian neurodegeneration comprises a heterogeneous neuropathology. Clinical labeling of patients with both dementia and Parkinson disease is dichotomous, depending on the temporal development of cognitive impairment and motor parkinsonism. Patients with dementia arising first (or within the first year of PD) are classified as dementia with Lewy bodies; patients with PD for more than one year before cognitive decline are classified as Parkinson disease with dementia. Despite this differential clinical classification, autopsy studies demonstrate variable admixtures of cortical synuicleinopathy, Aß-amyloidopathy and tau neurofibrillary tangle deposition. There are no routine clinical diagnostic measures that accurately distinguish the underlying neuropathologies in individual patients. In the present paper, we review the published literature describing characteristics of fibrillary Aß-amyloid deposition on the basis of PET radiotracer imaging in patients with Parkinson disease and in parkinsonian dementia syndromes. Although individual reports often include only small-to-modest subject numbers, there is overall suggestion that PD patients have a lower incidence of Aß-amyloid deposition than seen amongst elderly normal subjects, and that Parkinson disease with dementia patients have a lower incidence of Aß-amyloid deposition than do patients with dementia with Lewy bodies. These apparent features contrast the findings of Aß-amyloid-PET imaging in normal aging and the development of Alzheimer disease, where Aß-amyloid deposition arises asymptomatically and apparently many years before development of signs or symptoms of dementia. It is proposed that focused, prospective studies are needed to further address and understand the complex role(s) of Aß-amyloid pathology in Parkinson disease, and that this understanding will be critical to the development of targeted disease-modifying therapy for dementia in PD.

Frequency of cholinergic and caudate nucleus dopaminergic deficits across the predemented cognitive spectrum of Parkinson disease and evidence of interaction effects.

IMPORTANCE: Little is known about the relative contributions of multisystem degenerative processes across the spectrum of predemented cognitive decline in Parkinson disease (PD). OBJECTIVE: To investigate the relative frequency of caudate nucleus dopaminergic and forebrain cholinergic deficits across a spectrum of cognitively impaired patients with PD to explore their relative, individual, and combined contributions to cognitive impairment in PD. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study at an academic movement disorders clinic that included a predominantly nondemented cohort of 143 patients with PD. The mean (SD) age of patients was 65.5 (7.4) years and the mean (SD) Hoehn and Yahr stage was 2.4 (0.6). MAIN OUTCOMES AND MEASURES: Binary classification of carbon 11-labeled [11C]PMP acetylcholinesterase and caudate nucleus [11C]DTBZ monoaminergic positron-emission tomography imaging based on normative data. The frequency of significant degenerative processes based on normative values was determined for consecutive intervals of cognitive impairment, ranging from no or minimal (z > -0.5) to more severe (z ≤ -2) cognitive impairment. RESULTS: Across the spectrum from minimal (z > -0.5) to more severe (z ≤ -2) global cognitive impairment scores, caudate nucleus dopaminergic denervation was relatively frequent in individuals with minimal or no cognitive changes (51.1%) and increased in patients with more severe cognitive impairments (χ2 = 12.8; P = .01). Cortical cholinergic denervation frequency increased monotonically with increasing cognitive impairment from 24.7% (z > -0.5) to 85.7% (z ≤ -2); χ2 = 23.2; P = .001). Eighty-seven percent of patients with neocortical cholinergic deficits had caudate nucleus dopaminergic deficits. Multiple regression analysis (F = 7.51; P < .001) showed both independent cognitive predictions for caudate nucleus dopaminergic (F = 7.25; P = .008) and cortical cholinergic (F = 7.50; P = .007) degenerations as well as interaction effects (F = 5.40; P = .02). CONCLUSIONS AND RELEVANCE: Cortical cholinergic denervation is a major neurodegeneration associated with progressive declines across the spectrum of cognitive impairment in PD and typically occurs in the context of significant caudate nucleus dopaminergic denervation. Our findings imply that dopaminergic and cholinergic degenerations exhibit both independent and interactive contributions to cognitive impairment in PD.