John A Detre

• MD
• Professor at University of Pennsylvania

Obstructive sleep apnea (OSA) disrupts the oxygen supply during apneic and hypopneic events. To evaluate the feasibility of concurrently monitoring cerebral metabolic rate of oxygen (CMRO 2 ) and airway anatomy, a magnetic resonance imaging (MRI) pulse sequence was developed that interleaves measurements of CMRO 2 with anatomic imaging of the upper...

Brain development during adolescence and early adulthood coincides with shifts in emotion regulation and sleep. Despite this, few existing datasets simultaneously characterize affective dynamics, sleep variation, and multimodal measures of brain development. Here, we describe the study protocol and initial release (n = 10) of an open data resource...

Nuclear Overhauser effect (NOE) MRI has been used for in vivo brain imaging to assess lipid and protein composition and benefits from 7 T field strengths due to the larger chemical shift dispersion. However, a continuing challenge is signal drop off observed in regions such as the medial temporal lobes due to “standing wave” effects from shorter ra...

Multiple sclerosis is an inflammatory demyelinating condition of the central nervous system affecting approximately 1 million people in the USA. Although standard structural MRI techniques are now the main imaging modality for multiple sclerosis diagnosis and management, they are yet to provide information regarding the metabolic profile of the dis...

Background: The anterior portion of the medial temporal lobe (MTL) is one of the first regions targeted by pathology in sporadic Alzheimer's disease (AD) and Limbic-predominant Age-related TDP-43 Encephalopathy (LATE) indicating a potential for metrics from this region to serve as imaging biomarkers. Leveraging a unique post-mortem dataset of histo...

Background Opioid use disorder (OUD) has been linked to macroscopic structural alterations in the brain [1]. The monthly injectable, extended-release formulation of μ-opioid antagonist naltrexone (XR-NTX) is highly effective in reducing opioid craving and preventing opioid relapse [2,3]. Aims & Objectives We aimed to investigate the neuroanatomica...

Cerebral perfusion plays a crucial role in maintaining brain function and is tightly coupled with neuronal activity. While previous studies have examined cerebral perfusion trajectories across development and aging, precise characterization of its lifespan dynamics has been limited by small sample sizes and methodological inconsistencies. In this s...

Cerebral perfusion plays a crucial role in maintaining brain function and is tightly coupled with neuronal activity. While previous studies have examined cerebral perfusion trajectories across development and aging, precise characterization of its lifespan dynamics has been limited by small sample sizes and methodological inconsistencies. In this s...

Determining the level of consciousness in patients with brain injury-and more fundamentally, establishing what they can experience-is ethically and clinically impactful. Patient behaviors may unreliably reflect their level of consciousness: a subset of unresponsive patients demonstrate covert consciousness by willfully modulating their brain activi...

Tau exhibits change in both spatial extent and density of pathology along the Alzheimer's disease (AD) spectrum with each aspect contributing to the overall burden of pathological tau. Nevertheless, studies using Tau PET have measured either magnitude using standardized uptake value ratios (SUVRs) or extent using number of Tau+ regions. We hypothes...

Background Measures of tau burden have typically relied upon measures of magnitude, such as mean standardized uptake value ratio (SUVR), or extent, such as number of tau positive regions. However, heterogenous patterns of tau spread and accumulation present challenges to using these measures in isolation to quantify tau burden. Therefore, we hypoth...

Background Histopathological analysis of autopsied brains is the gold standard of diagnosis in neurodegenerative disorders. Co‐registered histology and MRI scans aid in understanding pathology and structural features. Previous studies focused on the medial temporal lobe (MTL) for atrophy patterns in phosphorylated tau (p‐tau) pathology and in whole...

Background Cerebral small vessel disease (CSVD) is the most prevalent cause of vascular cognitive impairment. Executive function impairment and white matter (WM) lesions occur early in CSVD, the latter typically in periventricular WM (PVWM) ‐ the least perfused brain region. Accounting for vascular risk factors (VRF) and amyloid status in cognitive...

Background Postmortem MRI allows brain anatomy to be examined at high‐resolution linking pathology with morphometric measurements. However, automated methods for analyzing postmortem MRI are not well developed. We present a deep learning‐based framework for automated segmentation of cortical mantle, subcortical structures (caudate, putamen, globus...

Background The extent to which pathological processes in aging and Alzheimer’s disease (AD) relate to functional alterations in the medial temporal lobe (MTL)‐dependent brain networks is poorly understood. Here, we examined the relationship between tau accumulation in the (trans)entorhinal cortex and functional connectivity (FC) in two MTL‐affiliat...

Background Previous work suggests functional abnormalities in the human brain in preclinical Alzheimer’s disease. However, little has been explored about the relationship between BOLD fMRI signal amplitude/energy over time and AD pathology. In this work we analyzed the effects of AD progression on amplitude of low‐frequency fluctuations (ALFF) duri...

Background Population‐based functional connectomes help explain heterogeneity in tau spread in Alzheimer’s disease by demonstrating spread among connected neurons from canonical epicenters. However, if the hypothesis of cell‐to‐cell transmission of tau is correct, individual structural connectomes seeded from individual‐specific epicenters of PET‐t...

Background The anterior portion of the MTL is one of the first regions targeted by pathology in sporadic Alzheimer’s disease (AD) indicating the potential for imaging metrics from this region to serve as valuable imaging biomarkers. However, most existing automated approaches for MTL segmentation do not incorporate anterior MTL subregions, and the...

Background Cerebral small vessel disease (CSVD) is the most prevalent cause of vascular cognitive impairment. Executive function impairment and white matter (WM) lesions occur early in CSVD, the latter typically in periventricular WM (PVWM) ‐ the least perfused brain region. Accounting for vascular risk factors (VRF) and amyloid status in cognitive...

Background Postmortem MRI allows brain anatomy to be examined at high‐resolution linking pathology with morphometric measurements. However, automated methods for analyzing postmortem MRI are not well developed. We present a deep learning‐based framework for automated segmentation of cortical mantle, subcortical structures (caudate, putamen, globus...

Background Previous work suggests functional abnormalities in the human brain in preclinical Alzheimer’s disease. However, little has been explored about the relationship between BOLD fMRI signal amplitude/energy over time and AD pathology. In this work we analyzed the effects of AD progression on amplitude of low‐frequency fluctuations (ALFF) duri...

Background The extent to which pathological processes in aging and Alzheimer’s disease (AD) relate to functional alterations in the medial temporal lobe (MTL)‐dependent brain networks is poorly understood. Here, we examined the relationship between tau accumulation in the (trans)entorhinal cortex and functional connectivity (FC) in two MTL‐affiliat...

Background Population‐based functional connectomes help explain heterogeneity in tau spread in Alzheimer’s disease by demonstrating spread among connected neurons from canonical epicenters. However, if the hypothesis of cell‐to‐cell transmission of tau is correct, individual structural connectomes seeded from individual‐specific epicenters of PET‐t...

Background Regional cerebral blood flow (CBF) can be noninvasively quantified using arterial spin labeled (ASL) perfusion MRI. In Alzheimer’s disease (AD) and mild cognitive impairment (MCI), hypoperfusion typically occurs in precuneus, posterior cingulate cortex (PCC), and hippocampus. Small vessel disease (SVD), a systemic disorder that commonly...

INTRODUCTION Alzheimer's disease (AD) typically involves both neurodegenerative and vascular pathologies, each associated with reductions in cerebral blood flow (CBF). However, it remains unclear whether vascular and neural contributions to regional CBF can be differentiated. METHODS Using 3D background‐suppressed arterial spin labeled perfusion m...

Functional magnetic resonance imaging (fMRI) using blood-oxygenation-level-dependent (BOLD) contrast relies on gradient echo echo-planar imaging (GE-EPI) to quantify dynamic susceptibility changes associated with the hemodynamic response to neural activity. However, acquiring BOLD fMRI in human olfactory regions is particularly challenging due to t...

The presence of multiple pathologies is the largest predictor of dementia. A major gap in the field is the in vivo detection of mixed pathologies and their antecedents. The Alzheimer's Disease Research Centers (ADRCs) are uniquely positioned to address this gap. The ADRCs longitudinally follow ≈ 17,000 participants, ranging from cognitively unimpai...

Functional MRI methods can assess aspects of drug-induced brain response. Resting blood oxygenation level dependent (BOLD) fMRI and arterial spin labeling (ASL) perfusion MRI indirectly measure brain function through the coupling of activity to cerebral blood flow (CBF) and oxygenation but their relative sensitivity has not been directly compared....

Functional magnetic resonance imaging (fMRI) offers an alternative to the traditional Wada test for presurgical language and memory lateralization that carries almost no risk. However, fMRI lateralization of episodic memory remains challenging because the hippocampus, which is fundamental to episodic memory, is smaller, more prone to susceptibility...

Alzheimer's disease (AD) is characterized by a long preclinical stage during which molecular markers of amyloid beta and tau pathology rise, but there is minimal neurodegeneration or cognitive decline. Previous literature suggests that measures of brain function might be more sensitive to neuropathologic burden during the preclinical stage of AD th...

Infant cerebral blood flow (CBF) delivers nutrients and oxygen to fulfill brain energy consumption requirements for the fastest period of postnatal brain development across the lifespan. However, organizing principle of whole-brain CBF dynamics during infancy remains obscure. Leveraging a unique cohort of 100+ infants with high-resolution arterial...

Understanding the neurophysiological changes that occur during loss and recovery of consciousness is a fundamental aim in neuroscience and has marked clinical relevance. Here, we utilize multimodal magnetic resonance neuroimaging to investigate changes in regional network connectivity and neurovascular dynamics as the brain transitions from wakeful...

INTRODUCTION Regional glucose hypometabolism resulting in glutamate loss has been shown as one of the characteristics of Alzheimer's disease (AD). Because the impact of AD varies between the sexes, we utilized glutamate‐weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) for high‐resolution spatial mapping of c...

The medial temporal lobe (MTL) is a hotspot for neuropathology, and measurements of MTL atrophy are often used as a biomarker for cognitive decline associated with neurodegenerative disease. Due to the aggregation of multiple proteinopathies in this region, the specific relationship of MTL atrophy to distinct neuropathologies is not well understood...

Purpose The purpose of this study was to determine the effect of acute nicotinamide riboside (NR) supplementation on cerebral nicotinamide adenine dinucleotide (NAD⁺) levels in the human brain in vivo by means of downfield proton MRS (DF ¹H MRS). Methods DF ¹H MRS was performed on 10 healthy volunteers in a 7.0 T MRI scanner with spectrally select...

Infant cerebral blood flow (CBF) delivers nutrients and oxygen to fulfill brain energy consumption requirements for the fastest period of postnatal brain development across the lifespan. However, organizing principle of whole-brain CBF dynamics during infancy remains obscure. Leveraging a unique cohort of 100 + infants with high-resolution arterial...

Our current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages of Alzheimer’s Disease (AD) is limited by the presence of confounding non-AD pathologies and the two-dimensional (2-D) nature of conventional histology studies. Here, we combine ex...

Background and Significance Positron Emission Tomography (PET) using fluorodeoxyglucose (FDG-PET) is a standard imaging modality for detecting areas of hypometabolism associated with the seizure onset zone (SOZ) in temporal lobe epilepsy (TLE). However, FDG-PET is costly and involves the use of a radioactive tracer. Arterial Spin Labeling (ASL) off...

Background: Volumetry of subregions in the medial temporal lobe (MTL) computed from automatic segmentation in MRI can track neurodegeneration in Alzheimer's disease. However, image quality may vary in MRI. Poor quality MR images can lead to unreliable segmentation of MTL subregions. Considering that different MRI contrast mechanisms and field stren...

INTRODUCTION Typical MRI measures of neurodegeneration have limited sensitivity in early disease stages. Diffusion MRI (dMRI) microstructural measures may allow for detection in preclinical stages. METHODS Participants had dMRI and either beta‐amyloid PET or plasma biomarkers of Alzheimer's pathology within 18 months of MRI. Microstructure was mea...

Postmortem MRI allows brain anatomy to be examined at high resolution and to link pathology measures with morphometric measurements. However, automated segmentation methods for brain mapping in postmortem MRI are not well developed, primarily due to limited availability of labeled datasets, and heterogeneity in scanner hardware and acquisition prot...

Infant cerebral blood flow (CBF) delivers nutrients and oxygen to fulfill brain energy consumption requirements for the fastest period of postnatal brain development across lifespan. However, organizing principle of whole-brain CBF dynamics during infancy remains obscure. Leveraging a unique cohort of 100+ infants with high-resolution arterial spin...

Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision‐making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi‐timepoint arterial spin labeling (ASL), along with recomm...

Regional cerebral blood flow (CBF) changes quantified using arterial spin labeling (ASL) are altered in neurodegenerative disorders such as frontotemporal lobar degeneration due to tau (FTLD-tau), but the relationship between ASL CBF and pathologic burden has not been assessed. Our objective was to determine whether regional ASL CBF acquired antemo...

Purpose Ultrahigh field (≥7 T) MRI is at the cutting edge of medical imaging, enabling enhanced spatial and spectral resolution as well as enhanced susceptibility contrast. However, transmit (B1+$$ {\mathrm{B}}_1^{+} $$) field inhomogeneity due to standing wave effects caused by the shortened RF wavelengths at 7 T is still a challenge to overcome....

A key function of sleep is to provide a regular period of reduced brain metabolism, which is critical for maintenance of healthy brain function. The purpose of this work was to quantify the sleep‐stage‐dependent changes in brain energetics in terms of cerebral metabolic rate of oxygen (CMRO 2 ) as a function of sleep stage using quantitative magnet...

Background Arterial spin labeling (ASL) derived cerebral blood flow (CBF) maps are prone to artifacts and noise that can degrade image quality. Purpose To develop an automated and objective quality evaluation index (QEI) for ASL CBF maps. Study Type Retrospective. Population Data from N = 221 adults, including patients with Alzheimer's disease (...

Background The anterior portion of the medial temporal lobe (MTL) is one of the earliest regions showing tau deposition in Alzheimer’s disease (AD) and hence a key focus area for AD imaging biomarkers. However, the anatomical variability of the anterior MTL presents a challenge for segmentation protocols. Leveraging a novel postmortem dataset with...

Background Despite the strengths conventional structural imaging measures to detect atrophy, cross‐sectional relationships between neurodegeneration and Alzheimer’s disease (AD) biomarkers in early stages is limited. Neurite orientation dispersion and density imaging (NODDI) measures microstructural alterations that are unique from conventional str...

Background The extent to which pathological processes in aging and Alzheimer’s disease (AD) relate to functional disruption of the medial temporal lobe (MTL)‐dependent brain networks is poorly understood. To address this knowledge gap, we examined functional connectivity (FC) alterations between anterior and posterior regions of the MTL and in MTL‐...

Background Accumulation of tau neurofibrillary tangles (NFT) in the medial temporal lobe (MTL) is an early pathological change associated with neurodegeneration in Alzheimer’s Disease (AD). Current understanding of the spread of NFTs within the MTL is based on 2‐D histological sections sampled at sparse locations. Here, using human MTL specimens fr...

Background Obstructive sleep apnea (OSA), which results from recurrent collapses of the upper airway system, affects around 27% of the geriatric population with mild cognitive impairment (MCI) and causes intermittent hypoxia and sleep fragmentation (Mubashir et al., 2019). Prior research suggests that OSA results in brain ischemic preconditioning,...

Background The extent to which pathological processes in aging and Alzheimer’s disease (AD) relate to functional disruption of the medial temporal lobe (MTL)‐dependent brain networks is poorly understood. To address this knowledge gap, we examined functional connectivity (FC) alterations between anterior and posterior regions of the MTL and in MTL‐...

Background Despite the strengths conventional structural imaging measures to detect atrophy, cross‐sectional relationships between neurodegeneration and Alzheimer’s disease (AD) biomarkers in early stages is limited. Neurite orientation dispersion and density imaging (NODDI) measures microstructural alterations that are unique from conventional str...

Introduction Endovascular therapy (EVT) has revolutionized acute stroke treatment, but large vessel recanalization does not always result in tissue‐level reperfusion. Cerebral blood flow (CBF) is not routinely monitored during EVT. Here we aimed to leverage diffuse correlation spectroscopy (DCS), a novel transcranial optical imaging technique, to a...

Sleep loss impacts a broad range of brain and cognitive functions. However, how sleep deprivation affects risky decision‐making remains inconclusive. This study used functional MRI to examine the impact of one night of total sleep deprivation (TSD) on risky decision‐making behavior and the underlying brain responses in healthy adults. In this study...

Background Endovascular therapy (EVT) has revolutionized the treatment of acute stroke, but large vessel recanalization does not always result in tissue-level reperfusion. Cerebral blood flow (CBF) is not routinely monitored during EVT. We aimed to leverage diffuse correlation spectroscopy (DCS), a novel transcranial optical imaging technique, to a...

Non-invasive methods of detecting early-stage Alzheimer’s disease (AD) can provide valuable insight into disease pathology, improving the diagnosis and treatment of AD. Nuclear Overhauser enhancement (NOE) MRI is a technique that provides image contrast sensitive to lipid and protein content in the brain. These macromolecules have been shown to be...

Functional disruption of the medial temporal lobe-dependent networks is thought to underlie episodic memory deficits in aging and Alzheimer’s disease. Previous studies revealed that the anterior medial temporal lobe is more vulnerable to pathological and neurodegenerative processes in Alzheimer’s disease. In contrast, cognitive and structural imagi...

Objective White matter hyperintensities (WMH) are commonly seen on T2-weighted magnetic resonance imaging (MRI) in older adults and are associated with an increased risk of cognitive decline and dementia. This study aims to estimate changes in the structural connectome due to age-related WMH by using a virtual lesion approach. Methods High-quality...

Background: Numerous studies summarized in a recent meta-analysis have shown sleep deprivation rapidly improves depressive symptoms in approximately 50 % of individuals with major depressive disorder (MDD), however those studies were typically conducted in clinical settings. Here we investigated the effects of sleep deprivation utilizing a highly...

Sleep loss robustly disrupts mood and emotion regulation in healthy individuals but can have a transient antidepressant effect in a subset of patients with depression. The neural mechanisms underlying this paradoxical effect remain unclear. Previous studies suggest that the amygdala and dorsal nexus (DN) play key roles in depressive mood regulation...

Importance: Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects nearly one million people in the United States. Up to 50% of patients with MS experience depression. Objective: To investigate how white matter network disruption is related to depression in MS. Design: Retrospective case-control study of participants who r...

When developing tools for automated cortical segmentation, the ability to produce topologically correct segmentations is important in order to compute geometrically valid morphometry measures. In practice, accurate cortical segmentation is challenged by image artifacts and the highly convoluted anatomy of the cortex itself. To address this, we prop...

Purpose Nuclear Overhauser effect magnetization transfer ratio (NOEMTR) is a technique used to investigate brain lipids and macromolecules in greater detail than other techniques and benefits from increased contrast at 7 T. However, this contrast can become degraded because of B1+$$ {\mathrm{B}}_1^{+} $$ inhomogeneities present at ultra‐high field...

Resting-state functional magnetic resonance imaging (fMRI) with graph theoretical modeling has been increasingly applied for assessing whole brain network topological organization, yet its reproducibility remains controversial. In this study, we acquired three repeated resting-state fMRI scans from 16 healthy controls during a strictly controlled i...

White matter hyperintensity (WMH) lesions on T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and changes in adjacent normal-appearing white matter can disrupt computerized tract reconstruction and result in inaccurate measures of structural brain connectivity. The virtual lesion approach provides an alternative strat...

Purpose To monitor the metabolic turnover of β‐hydroxybutyrate (BHB) oxidation using ²H‐MRS in conjunction with intravenous administration of ²H labeled BHB. Methods Nine‐month‐old mice were infused with [3,4,4,4]‐²H4‐BHB (d4‐BHB; 3.11 g/kg) through the tail vein using a bolus variable infusion rate for a period of 90 min. The labeling of downstre...

Ex vivo MRI of the brain provides remarkable advantages over in vivo MRI for visualizing and characterizing detailed neuroanatomy, and helps to link microscale histology studies with morphometric measurements. However, automated segmentation methods for brain mapping in ex vivo MRI are not well developed, primarily due to limited availability of la...

Sleep, a state of reduced consciousness, affects brain oxygen metabolism and lowers cerebral metabolic rate of oxygen (CMRO2). Previously, we quantified CMRO2 during sleep via Fick's Principle, with a single-band MRI sequence measuring both hemoglobin O2 saturation (SvO2) and superior sagittal sinus (SSS) blood flow, which was upscaled to obtain to...

When developing tools for automated cortical segmentation, the ability to produce topologically correct segmentations is important in order to compute geometrically valid morphometry measures. In practice, accurate cortical segmentation is challenged by image artifacts and the highly convoluted anatomy of the cortex itself. To address this, we prop...

Importance Little is known about the associations of strict blood pressure (BP) control with microstructural changes in small vessel disease markers. Objective To investigate the regional associations of intensive vs standard BP control with small vessel disease biomarkers, such as white matter lesions (WMLs), fractional anisotropy (FA), mean diff...

Functional disruption of the medial temporal lobe-dependent networks is thought to underlie episodic memory deficits in aging and Alzheimer’s disease. Previous studies revealed that the anterior medial temporal lobe is more vulnerable to pathological and neurodegenerative processes in Alzheimer’s disease. In contrast, cognitive and structural imagi...

White matter hyperintensities (WMH) on FLAIR MRI are highly prevalent in older adults and are linked to cognitive deficits as well as dementia. Likely mechanisms underlying associations between WMH and cognitive deficits include widespread partial disconnection due to the diffuse nature of progressive WMH and/or tract‐specific disconnection syndrom...

Brain cortical microinfarcts (CMI) are negatively correlated with cognitive function in both normal aging and Alzheimer’s disease (AD). High‐field structural magnetic resonance imaging (MRI) has facilitated in vivo detection of CMIs but their significance and underlying pathological mechanism remain uncertain. Here we assessed correlations between...

Neurodegenerative disorders are associated with different pathologies that often co‐occur and have differential contribution to the pattern of cognitive impairment. The majority of these pathologies cannot be detected or measured by in‐vivo methods; therefore, recognition of the topographic patterns of them and association with MRI findings may pro...

Introduction: Neurodegenerative disorders are associated with different pathologies that often co-occur but cannot be measured specifically with in vivo methods. Methods: Thirty-three brain hemispheres from donors with an Alzheimer's disease (AD) spectrum diagnosis underwent T2-weighted magnetic resonance imaging (MRI). Gray matter thickness was...

Dimensionality reduction, a form of compression, can simplify representations of information to increase efficiency and reveal general patterns. Yet, this simplification also forfeits information, thereby reducing representational capacity. Hence, the brain may benefit from generating both compressed and uncompressed activity, and may do so in a he...

Background Metabolic and vascular risk factors (MVRF) are associated with neurodegeneration and poor cognition. There is a need to better understand the impact of these risk factors on brain health in the decades that precede cognitive impairment. Longitudinal assessments can provide new insight regarding changes in MVRFs that are related to brain...

Temporal lobe epilepsy (TLE) is one of the most common subtypes of focal epilepsy, with mesial temporal sclerosis (MTS) being a common radiological and histopathological finding. Accurate identification of MTS during presurgical evaluation confers an increased chance of good surgical outcome. Here we propose the use of glutamate‐weighted chemical e...