The differentiation of idiopathic Parkinson disease (IPD) from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), the most common atypical parkinsonian look-alike syndromes ...(APS), can be clinically challenging. In these disorders, diagnostic inaccuracy is more frequent early in the clinical course when signs and symptoms are mild. Diagnostic inaccuracy may be particularly relevant in trials of potential disease-modifying agents, which typically involve participants with early clinical manifestations. In an initial study, we developed a probabilistic algorithm to classify subjects with clinical parkinsonism but uncertain diagnosis based on the expression of metabolic covariance patterns for IPD, MSA, and PSP. Classifications based on this algorithm agreed closely with final clinical diagnosis. Nonetheless, blinded prospective validation is required before routine use of the algorithm can be considered.
We used metabolic imaging to study an independent cohort of 129 parkinsonian subjects with uncertain diagnosis; 77 (60%) had symptoms for 2 y or less at the time of imaging. After imaging, subjects were followed by blinded movement disorders specialists for an average of 2.2 y before final diagnosis was made. When the algorithm was applied to the individual scan data, the probabilities of IPD, MSA, and PSP were computed and used to classify each of the subjects. The resulting image-based classifications were then compared with the final clinical diagnosis.
IPD subjects were distinguished from APS with 94% specificity and 96% positive predictive value (PPV) using the original 2-level logistic classification algorithm. The algorithm achieved 90% specificity and 85% PPV for MSA and 94% specificity and 94% PPV for PSP. The diagnostic accuracy was similarly high (specificity and PPV > 90%) for parkinsonian subjects with short symptom duration. In addition, 25 subjects were classified as level I indeterminate parkinsonism and 4 more subjects as level II indeterminate APS.
Automated pattern-based image classification can improve the diagnostic accuracy in patients with parkinsonism, even at early disease stages.
Significance We present an innovative approach to evaluate default mode network (DMN) activity in individual subjects using metabolic imaging. After characterizing a distinct set of metabolic resting ...state networks (RSNs) in healthy subjects, network activity was tracked over time in patients with neurodegenerative disorders, such as Parkinson’s disease and Alzheimer’s disease. We found that the dominant normal metabolic RSN, which corresponded to the DMN, is preserved in early-stage Parkinson’s disease patients. Although significant DMN reductions developed later, these changes were reversible in part by dopamine treatment. This finding contrasts with Alzheimer’s disease, in which DMN loss is rapid and continuous, beginning before clinical diagnosis. Metabolic imaging can provide a versatile, quantitative means of assessing brain disease at the network level.
The delineation of resting state networks (RSNs) in the human brain relies on the analysis of temporal fluctuations in functional MRI signal, representing a small fraction of total neuronal activity. Here, we used metabolic PET, which maps nonfluctuating signals related to total activity, to identify and validate reproducible RSN topographies in healthy and disease populations. In healthy subjects, the dominant (first component) metabolic RSN was topographically similar to the default mode network (DMN). In contrast, in Parkinson’s disease (PD), this RSN was subordinated to an independent disease-related pattern. Network functionality was assessed by quantifying metabolic RSN expression in cerebral blood flow PET scans acquired at rest and during task performance. Consistent task-related deactivation of the “DMN-like” dominant metabolic RSN was observed in healthy subjects and early PD patients; in contrast, the subordinate RSNs were activated during task performance. Network deactivation was reduced in advanced PD; this abnormality was partially corrected by dopaminergic therapy. Time-course comparisons of DMN loss in longitudinal resting metabolic scans from PD and Alzheimer’s disease subjects illustrated that significant reductions appeared later for PD, in parallel with the development of cognitive dysfunction. In contrast, in Alzheimer’s disease significant reductions in network expression were already present at diagnosis, progressing over time. Metabolic imaging can directly provide useful information regarding the resting organization of the brain in health and disease.
Purpose
Tumor-associated macrophages (TAMs) are a key component of glioblastoma (GBM) microenvironment. Considering the differential role of different TAM phenotypes in iron metabolism with the M1 ...phenotype storing intracellular iron, and M2 phenotype releasing iron in the tumor microenvironment, we investigated MRI to quantify iron as an imaging biomarker for TAMs in GBM patients.
Methods
21 adult patients with GBM underwent a 3D single echo gradient echo MRI sequence and quantitative susceptibility maps were generated. In 3 subjects, ex vivo imaging of surgical specimens was performed on a 9.4 Tesla MRI using 3D multi-echo GRE scans, and R2* (1/T2*) maps were generated. Each specimen was stained with hematoxylin and eosin, as well as CD68, CD86, CD206, and
l
-Ferritin.
Results
Significant positive correlation was observed between mean susceptibility for the tumor enhancing zone and the
l
-ferritin positivity percent (r = 0.56, p = 0.018) and the combination of tumor’s enhancing zone and necrotic core and the
l
-Ferritin positivity percent (r = 0.72; p = 0.001). The mean susceptibility significantly correlated with positivity percent for CD68 (ρ = 0.52, p = 0.034) and CD86 (r = 0.7 p = 0.001), but not for CD206 (ρ = 0.09; p = 0.7). There was a positive correlation between mean R2* values and CD68 positive cell counts (r = 0.6, p = 0.016). Similarly, mean R2* values significantly correlated with CD86 (r = 0.54, p = 0.03) but not with CD206 (r = 0.15, p = 0.5).
Conclusions
This study demonstrated the potential of MR quantitative susceptibility mapping as a non-invasive method for in vivo TAM quantification and phenotyping. Validation of these findings with large multicenter studies is needed.
Alzheimer's disease remains incurable, and the failures of current disease-modifying strategies for Alzheimer's disease could be attributed to a lack of in vivo models that recapitulate the ...underlying etiology of late-onset Alzheimer's disease. The etiology of late-onset Alzheimer's disease is not based on mutations related to amyloid-β (Aβ) or tau production which are currently the basis of in vivo models of Alzheimer's disease. It has recently been suggested that mechanisms like chronic neuroinflammation may occur prior to amyloid-β and tau pathologies in late-onset Alzheimer's disease. The aim of this study is to analyze the characteristics of rodent models of neuroinflammation in late-onset Alzheimer's disease. Our search criteria were based on characteristics of an idealistic disease model that should recapitulate causes, symptoms, and lesions in a chronological order similar to the actual disease. Therefore, a model based on the inflammation hypothesis of late-onset Alzheimer's disease should include the following features: (i) primary chronic neuroinflammation, (ii) manifestations of memory and cognitive impairment, and (iii) late development of tau and Aβ pathologies. The following models fit the pre-defined criteria: lipopolysaccharide- and PolyI:C-induced models of immune challenge; streptozotocin-, okadaic acid-, and colchicine neurotoxin-induced neuroinflammation models, as well as interleukin-1β, anti-nerve growth factor and p25 transgenic models. Among these models, streptozotocin, PolyI:C-induced, and p25 neuroinflammation models are compatible with the inflammation hypothesis of Alzheimer's disease.
The heterogeneity of behavioral variant frontotemporal dementia (bvFTD) calls for multivariate imaging biomarkers.
We studied a total of 148 dementia patients from the Feinstein Institute (Center-A: ...25 bvFTD and 10 Alzheimer's disease), Technical University of Munich (Center-B: 44 bvFTD and 29 FTD language variants), and Alzheimer's Disease Neuroimaging Initiative (40 Alzheimer's disease subjects). To identify the covariance pattern of bvFTD (behavioral variant frontotemporal dementia–related pattern bFDRP), we applied principal component analysis to combined 18F-fluorodeoxyglucose–positron emission tomography scans from bvFTD and healthy subjects. The phenotypic specificity and clinical correlates of bFDRP expression were assessed in independent testing sets.
The bFDRP was identified in Center-A data (24.1% of subject × voxel variance; P < .001), reproduced in Center-B data (P < .001), and independently validated using combined testing data (receiver operating characteristics–area under the curve = 0.97; P < .0001). The expression of bFDRP was specifically elevated in bvFTD patients (P < .001) and was significantly higher at more advanced disease stages (P = .035:duration; P < .01:severity).
The bFDRP can be used as a quantitative imaging marker to gauge the underlying disease process and aid in the differential diagnosis of bvFTD.
Characteristics of the neighborhood built environment influence health and health behavior. Google Street View (GSV) images may facilitate measures of the neighborhood environment that are ...meaningful, practical, and adaptable to any geographic boundary. We used GSV images and computer vision to characterize neighborhood environments (green streets, visible utility wires, and dilapidated buildings) and examined cross-sectional associations with chronic health outcomes among patients from the University of California, San Francisco Health system with outpatient visits from 2015 to 2017. Logistic regression models were adjusted for patient age, sex, marital status, race/ethnicity, insurance status, English as preferred language, assignment of a primary care provider, and neighborhood socioeconomic status of the census tract in which the patient resided. Among 214,163 patients residing in California, those living in communities in the highest tertile of green streets had 16-29% lower prevalence of coronary artery disease, hypertension, and diabetes compared to those living in communities in the lowest tertile. Conversely, a higher presence of visible utility wires overhead was associated with 10-26% more coronary artery disease and hypertension, and a higher presence of dilapidated buildings was associated with 12-20% greater prevalence of coronary artery disease, hypertension, and diabetes. GSV images and computer vision models can be used to understand contextual factors influencing patient health outcomes and inform structural and place-based interventions to promote population health.
Capillary hemangiomas are rare vascular lesions that rarely affect the central nervous system. When they present within the spinal canal, they are typically confined intradurally, with intramedullary ...extension rare. We present a rare case of spinal intramedullary capillary hemangioma, with a systematic review of the literature.
Medical records and imaging data were retrospectively reviewed using the health record software EPIC (Verona, Wisconsin, USA) and the radiology management software system RIS/PACS (Radiology Information System/Picture Archiving and Communication System; QREADS). The report was written in accordance with the CARE (case reports) guidelines. We also performed a systematic review of the literature on all cases of intramedullary spinal capillary hemangiomas in accordance with PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines.
We report a case of a 54-year-old man who presented with progressive paraplegia and sensory deficits in the lower extremities. Spinal magnetic resonance imaging showed an intramedullary enhancing lesion centered at T11 with associated spinal cord compression. He underwent thoracic laminectomy and gross total resection of the lesion without complications and subsequent improvement on his neurological examination. Histological examination showed findings consistent with a capillary hemangioma. The literature review also documented 21 studies with a combined total of 38 cases of intramedullary spinal capillary hemangioma.
Purely intramedullary capillary hemangiomas are unusual spinal lesions with only a few cases reported in the literature. These should be considered in the differential diagnosis of intramedullary tumors. Surgical management remains the first line of treatment for symptomatic patients.
To determine whether cognitive impairment in Parkinson disease (PD) and Alzheimer disease (AD) derives from the same network pathology.
We analyzed
F-fluorodeoxyglucose PET scans from 40 patients ...with AD and 40 age-matched healthy controls from the Alzheimer's Disease Neuroimaging Initiative and scanned an additional 10 patients with AD and 10 healthy controls at The Feinstein Institute for Medical Research to derive an AD-related metabolic pattern (ADRP) analogous to our previously established PD cognition-related pattern (PDCP) and PD motor-related pattern (PDRP). We computed individual subject expression values for ADRP and PDCP in 89 patients with PD and correlated summary scores for cognitive functioning with network expression. We also evaluated changes in ADRP and PDCP expression in a separate group of 15 patients with PD scanned serially over a 4-year period.
Analysis revealed a significant AD-related metabolic topography characterized by covarying metabolic reductions in the hippocampus, parahippocampal gyrus, and parietal and temporal association regions. Expression of ADRP, but not PDCP, was elevated in both AD groups and correlated with worse cognitive summary scores. Patients with PD showed slight ADRP expression, due to topographic overlap with the network underlying PD motor-related pattern degeneration, but only their PDCP expression values increased as cognitive function and executive performance declined. Longitudinal data in PD disclosed an analogous dissociation of network expression.
Cognitive dysfunction in PD is associated with a specific brain network that is largely spatially and functionally distinct from that seen in relation to AD.
Collecting neighborhood data can both be time- and resource-intensive, especially across broad geographies. In this study, we leveraged 1.4 million publicly available Google Street View (GSV) images ...from Utah to construct indicators of the neighborhood built environment and evaluate their associations with 2017-2019 health outcomes of approximately one-third of the population living in Utah. The use of electronic medical records allows for the assessment of associations between neighborhood characteristics and individual-level health outcomes while controlling for predisposing factors, which distinguishes this study from previous GSV studies that were ecological in nature. Among 938,085 adult patients, we found that individuals living in communities in the highest tertiles of green streets and non-single-family homes have 10-27% lower diabetes, uncontrolled diabetes, hypertension, and obesity, but higher substance use disorders-controlling for age, White race, Hispanic ethnicity, religion, marital status, health insurance, and area deprivation index. Conversely, the presence of visible utility wires overhead was associated with 5-10% more diabetes, uncontrolled diabetes, hypertension, obesity, and substance use disorders. Our study found that non-single-family and green streets were related to a lower prevalence of chronic conditions, while visible utility wires and single-lane roads were connected with a higher burden of chronic conditions. These contextual characteristics can better help healthcare organizations understand the drivers of their patients' health by further considering patients' residential environments, which present both risks and resources.
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