MISPEL: A supervised deep learning harmonization method for multi-scanner neuroimaging data.

Large-scale data obtained from aggregation of already collected multi-site neuroimaging datasets has brought benefits such as higher statistical power, reliability, and robustness to the studies. Despite these promises from growth in sample size, substantial technical variability stemming from differences in scanner specifications exists in the aggregated data and could inadvertently bias any downstream analyses on it. Such a challenge calls for data normalization and/or harmonization frameworks, in addition to comprehensive criteria to estimate the scanner-related variability and evaluate the harmonization frameworks.

Multi-scanner Harmonization of Paired Neuroimaging Data via Structure Preserving Embedding Learning.

Combining datasets from multiple sites/scanners has been becoming increasingly more prevalent in modern neuroimaging studies. Despite numerous benefits from the growth in sample size, substantial technical variability associated with site/scanner-related effects exists which may inadvertently bias subsequent downstream analyses. Such a challenge calls for a data harmonization procedure which reduces the scanner effects and allows the scans to be combined for pooled analyses.

ROBUST WHITE MATTER HYPERINTENSITY SEGMENTATION ON UNSEEN DOMAIN.

Typical machine learning frameworks heavily rely on an underlying assumption that training and test data follow the same distribution. In medical imaging which increasingly begun acquiring datasets from multiple sites or scanners, this identical distribution assumption often fails to hold due to systematic variability induced by site or scanner dependent factors. Therefore, we cannot simply expect a model trained on a given dataset to consistently work well, or generalize, on a dataset from another distribution.

MULTI-DOMAIN LEARNING BY META-LEARNING: TAKING OPTIMAL STEPS IN MULTI-DOMAIN LOSS LANDSCAPES BY INNER-LOOP LEARNING.

We consider a model-agnostic solution to the problem of Multi-Domain Learning (MDL) for multi-modal applications. Many existing MDL techniques are model-dependent solutions which explicitly require nontrivial architectural changes to construct domain-specific modules. Thus, properly applying these MDL techniques for new problems with well-established models, e.

A multi-scanner neuroimaging data harmonization using RAVEL and ComBat.

Modern neuroimaging studies frequently combine data collected from multiple scanners and experimental conditions. Such data often contain substantial technical variability associated with image intensity scale (image intensity scales are not the same in different images) and scanner effects (images obtained from different scanners contain substantial technical biases). Here we evaluate and compare results of data analysis methods without any data transformation (RAW), with intensity normalization using RAVEL, with regional harmonization methods using ComBat, and a combination of RAVEL and ComBat.

Characterization of point-spread function specification error on Geometric Transfer Matrix partial volume correction in [C]PiB amyloid imaging.

Purpose: Partial-volume correction (PVC) using the Geometric Transfer Matrix (GTM) method is used in positron emission tomography (PET) to compensate for the effects of spatial resolution on quantitation. We evaluate the effect of misspecification of scanner point-spread function (PSF) on GTM results in amyloid imaging, including the effect on amyloid status classification (positive or negative).

Methods: Twenty-nine subjects with Pittsburgh Compound B ([C]PiB) PET and structural T1 MR imaging were analyzed.

Validation of amyloid PET positivity thresholds in centiloids: a multisite PET study approach.

Background: Inconsistent positivity thresholds, image analysis pipelines, and quantitative outcomes are key challenges of multisite studies using more than one β-amyloid (Aβ) radiotracer in positron emission tomography (PET). Variability related to these factors contributes to disagreement and lack of replicability in research and clinical trials. To address these problems and promote Aβ PET harmonization, we used [F]florbetaben (FBB) and [F]florbetapir (FBP) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to derive (1) standardized Centiloid (CL) transformations and (2) internally consistent positivity thresholds based on separate young control samples.

Imaging beta-amyloid (Aβ) burden in the brains of middle-aged individuals with alcohol-use disorders: a [C]PIB PET study.

No in vivo human studies have examined the prevalence of Alzheimer's disease (AD) neuropathology in individuals with alcohol-use disorder (AUD), although recent research suggests that a relationship between the two exists. Therefore, this study used Pittsburgh Compound-B ([C]PiB) PET imaging to test the hypothesis that AUD is associated with greater brain amyloid (Aβ) burden in middle-aged adults compared to healthy controls. Twenty healthy participants (14M and 6F) and 19 individuals with AUD (15M and 4F), all aged 40-65 years, underwent clinical assessment, MRI, neurocognitive testing, and positron emission tomography (PET) imaging.

Direct Comparison of the Tau PET Tracers F-Flortaucipir and F-MK-6240 in Human Subjects.

Tau PET tracers exhibit varying levels of specific signal and distinct off-target binding patterns that are more diverse than amyloid PET tracers. This study compared 2 frequently used tau PET tracers, F-flortaucipir and F-MK-6240, in the same subjects. F-flortaucipir and F-MK-6240 scans were collected within 2 mo in 15 elderly subjects varying in clinical diagnosis and cognition.

Alzheimer's disease pathology in a community-based sample of older adults without dementia: The MYHAT neuroimaging study.

A true understanding of the distribution and functional correlates of Alzheimer's disease pathology in dementia-free older adults requires a population-based perspective. Here we report initial findings from a sample of 102 cognitively unimpaired participants (average age 77.2 years, 54.

Influence of apolipoprotein-E genotype on brain amyloid load and longitudinal trajectories.

To characterize the influence of apolipoprotein-E (APOE) genotype on cerebral Aβ load and longitudinal Aβ trajectories, [C]Pittsburgh compound-B (PiB) positron emission tomography (PET) imaging was used to assess amyloid load in a clinically heterogeneous cohort of 428 elderly participants with known APOE genotype. Serial [C]PiB data and a repeated measures model were used to model amyloid trajectories in a subset of 235 participants classified on the basis of APOE genotype. We found that APOE-ε4 was associated with increased Aβ burden and an earlier age of onset of Aβ positivity, whereas APOE-ε2 appeared to have modest protective effects against Aβ.

Amyloid accumulation in Down syndrome measured with amyloid load.

Introduction: Individuals with Down syndrome (DS) show enhanced amyloid beta (Aβ) deposition in the brain. A new positron emission tomography (PET) index of amyloid load ( ) was recently developed as an alternative to standardized uptake value ratios (SUVrs) to quantify Aβ burden with high sensitivity for detecting and tracking Aβ change..

Associations between NIH Toolbox Cognition Battery and brain amyloid and tau pathology in non-demented older adults.

Introduction: The National Institutes of Health (NIH) Toolbox Cognition Battery (NIHTB-CB) was developed to be a common assessment metric across a broad array of research studies. We investigated associations between NIHTB-CB and brain amyloid and tau deposition in cognitively unimpaired older adults.

Methods: One hundred eighteen community-based volunteers completed magnetic resonance imaging (MRI), Pittsburgh compound B (PiB)-PET (positron emission tomography) and AV-1451-PET neuroimaging, a neuropsychological evaluation, NIHTB-CB, and the Clinical Dementia Rating (CDR) scale.

[F]FDG, [C]PiB, and [F]AV-1451 PET Imaging of Neurodegeneration in Two Subjects With a History of Repetitive Trauma and Cognitive Decline.

Trauma-related neurodegeneration can be difficult to differentiate from multifactorial neurodegenerative syndromes, both clinically and radiographically. We have initiated a protocol for imaging of patients with suspected TBI-related neurodegeneration utilizing volumetric MRI and PET studies, including [F]FDG indexing cerebral glucose metabolism, [C]PiB for Aβ deposition, and [F]AV-1451 for tau deposition. To present results from a neuroimaging protocol for evaluation of TBI-related neurodegeneration in patients with early-onset cognitive decline and a history of TBI.

Comparison of longitudinal Aβ in nondemented elderly and Down syndrome.

Down syndrome (DS) predisposes individuals to early Alzheimer's disease (AD). Using Pittsburgh Compound B ([C]PiB), a pattern of striatal amyloid beta (Aβ) that is elevated relative to neocortical binding has been reported, similar to that of nondemented autosomal dominant AD mutation carriers. However, it is not known whether changes in striatal and neocortical [C]PiB retention differ over time in a nondemented DS population when compared to changes in a nondemented elderly (NDE) population.

Impact of partial volume correction on the regional correspondence between in vivo [C-11]PiB PET and postmortem measures of Aβ load.

The positron emission tomography (PET) radiotracer Pittsburgh Compound B ([C-11]PiB) demonstrates a high affinity for fibrillary amyloid-beta (Aβ) aggregates. However, [C-11]PiB's in vivo sensitivity and specificity is an ongoing area of investigation in correlation studies with postmortem measures of Aβ pathology. One potential confound in PET-to-postmortem correlation studies is the limited spatial resolution of PET and resulting partial volume effects (PVEs).

The use of Centiloids for applying [C]PiB classification cutoffs across region-of-interest delineation methods.

Introduction: Centiloid standardization was developed to establish a quantitative outcome measure of amyloid burden that could accommodate the integration of different amyloid positron emission tomography radiotracers or different methods of quantifying the same tracer. The goal of this study was to examine the use of Centiloids for establishing amyloid classification cutoffs for differing region-of-interest (ROI) delineation schemes.

Methods: Using ROIs from hand-drawn delineation in native space as the gold standard, we compared standard uptake value ratios obtained from the 6 hand-drawn ROIs that determine amyloid-positivity classification with standard uptake value ratio obtained from 3 different automated techniques (FreeSurfer, Statistical Parametric Mapping, and superimposed hand-drawn ROIs in Pittsburgh Compound B template space).

Image-Based 2D Re-Projection for Attenuation Substitution in PET Neuroimaging.

Purpose: In dual modality positron emission tomography (PET)/magnetic resonance imaging (MRI), attenuation correction (AC) methods are continually improving. Although a new AC can sometimes be generated from existing MR data, its application requires a new reconstruction. We evaluate an approximate 2D projection method that allows offline image-based reprocessing.

Dynamic PET imaging reveals heterogeneity of skeletal muscle insulin resistance.

Purpose: Skeletal muscle insulin resistance (IR) often precedes hyperglycemia and type 2 diabetes. However, variability exists within different skeletal muscle types and can be influenced by 3 primary steps of control: glucose delivery, transport, and phosphorylation. We performed dynamic positron emission tomography imaging studies to determine the extent to which heterogeneity in muscle type and control of insulin action contribute to IR.

Percutaneous intracerebral navigation by duty-cycled spinning of flexible bevel-tipped needles.

Background: Intracerebral drug delivery using surgically placed microcatheters is a growing area of interest for potential treatment of a wide variety of neurological diseases, including tumors, neurodegenerative disorders, trauma, epilepsy, and stroke. Current catheter placement techniques are limited to straight trajectories. The development of an inexpensive system for flexible percutaneous intracranial navigation may be of significant clinical benefit.

Modeling of needle steering via duty-cycled spinning.

As flexible bevel tip needles are inserted into tissue, a deflection force causes the needle to bend with a curvature dependent on relative stiffness and bevel angle. By constantly spinning the needle during insertion, the bevel angle is essentially negated and a straight trajectory can be achieved. Incorporating duty-cycled spinning during needle insertion provides proportional control of the curvature of the needle trajectory through tissue.