About

D.S. Fahmeed Hyder is a Professor of Biomedical Engineering at Yale University, with additional appointments in Radiology & Biomedical Imaging. His research focuses on developing quantitative and translational imaging technologies, primarily based on magnetic resonance methods, to visualize molecular processes of function and dysfunction at the laminar level. A primary interest in his laboratory is to develop functional imaging techniques that relate neural activity to underlying laminar structure in health and disease. He is also actively involved in molecular imaging with magnetic resonance technologies, connecting disciplines from chemistry and physics to material science and physiology. Hyder's work addresses the societal burden of misdiagnosed brain disorders and diseases by leading breakthroughs in imaging technologies that enhance understanding of brain function and pathology.

Research topics

• Medicine
• Computer Science
• Artificial Intelligence
• Biology
• Chemistry
• Pathology
• Nanotechnology
• Nuclear magnetic resonance
• Machine Learning
• Materials science
• Neuroscience
• Internal medicine
• Physics
• Optics
• Polymer chemistry
• Psychology
• Cancer research
• Endocrinology
• Physiology
• Chemical engineering
• Chromatography
• Pharmacology

Selected publications

• High-resolution thermal imaging to delineate effects of cancer-induced aerobic glycolysis and endothelial dysfunction

  Neuro-Oncology Advances · 2026-01-01

  articleOpen accessSenior author

  Abstract Background Glioblastoma multiforme (GBM) is an aggressive brain tumor with abysmal prognosis because cancer cell growth in the tumor microenvironment (TME) is orchestrated by complex interplay between aerobic glycolysis (AG) and endothelial dysfunction (ED). AG acidifies extracellular pH (pHe) to promote tumor invasion and suppress immune response, whereas ED leads to leaky blood vessels which hampers perfusion and stimulates hypoxia. Since metabolism generates heat and perfusion removes heat, we hypothesized that temperature could reflect both metabolic and vascular reprogramming in the TME mediated by AG and ED. Methods We used multiple magnetic resonance methods and bioheat modeling to dissect temperature contributions from metabolic and vascular sources in rat gliomas. Results Upregulated AG in the TME results from enhanced glycolysis (∼4.2× higher) and reduced glucose oxidation (∼4.8× lower), which leads to more acidic pHe (6.9 ± 0.1 vs 7.3 ± 0.1). Since TME is hypoperfused (∼40% lower) and glycolysis is less exothermic compared to glucose oxidation, simulations predict a cooler TME as in vivo measurements clearly demonstrate (0.5-1.5 °C). Moreover, temperature and pHe are correlated both inside and outside the TME for untreated and treated rats (r > 0.6). Conclusions Since TME is more glycolytic, acidic, hypoperfused, and cooler than neighboring milieu, thermal mapping can represent combined effects of AG and ED for early GBM detection and therapy optimization.

  PublisherDOI

• Supporting raw data scores for figures 1-7 and supplemental figures S1-S5

  Figshare · 2026-05-02

  datasetOpen access

  These data include the raw values underlying Figures 1–7 and Supplementary Figures S1–S5, as well as resting-state fMRI images (NIfTI-formatted; Fig. 6) for the manuscript “The Microglial TREM2 Receptor Programs Hippocampal Development in a Mouse Model of Childhood Deprivation,” currently under review at <i>Biological Psychiatry</i> and available as a bioRxiv preprint (10.1101/2025.08.11.669425).

  PublisherDOI

• Supporting raw data scores for figures 1-7 and supplemental figures S1-S5

  Figshare · 2026-05-02

  datasetOpen access

  These data include the raw values underlying Figures 1–7 and Supplementary Figures S1–S5, as well as resting-state fMRI images (NIfTI-formatted; Fig. 6) for the manuscript “The Microglial TREM2 Receptor Programs Hippocampal Development in a Mouse Model of Childhood Deprivation,” currently under review at <i>Biological Psychiatry</i> and available as a bioRxiv preprint (10.1101/2025.08.11.669425).

  PublisherDOI

• Abstract A028: A Robust and Reproducible Pipeline for Quantifying Stroke Injury in a Heterogeneous, Multi-Site Preclinical Network

  Stroke · 2026-01-29

  article

  Introduction: The failure to translate promising preclinical stroke therapies into clinical success is largely attributed to a lack of rigorous, reproducible outcome measures. While magnetic resonance imaging (MRI) offers a translational alternative to traditional histology, its use in large, multi-site trials is challenged by data heterogeneity and the need for scalable analysis. To address this, we developed and validated a fully automated, open-source image analysis pipeline for the Stroke Preclinical Assessment Network (SPAN), a six-center preclinical trial. Methods: T2 and ADC MRI scans were acquired from 2443 mice and rats (including aged and obese cohorts) at 6 centers 2 and 30 days after middle cerebral artery occlusion (MCAO). Our open-source pipeline performs a complete workflow ( Figure 1 ): 1) preprocessing (image reconstruction, denoising, parameter estimation and quality assessment measures); 2) intensity harmonization to reduce inter-site variability; 3) brain extraction using either traditional rule-based segmentation (rats) or U-net deep learning model (mice); 4) rule-based lesion segmentation via thresholding of harmonized T2 and ADC maps ( Figure 2A-G ); and 5) quantification of midline shift as a proxy for swelling and atrophy ( Figure 3A ). Validation was performed against expert manual tracing on both MRI and 2,3,5-Triphenyltetrazolium chloride (TTC)-stained tissue. Results: The pipeline successfully processed thousands of scans from a heterogeneous collection of scanners. The U-net brain extraction model was highly accurate (Dice score=0.964) and successfully segmented cases where traditional methods failed. Automated lesion volumes correlated strongly with manual expert MRI tracing (R=0.957) and with TTC staining in optimal preparations (R=0.86; Figure 2H ). Harmonization significantly reduced site-specific differences in MRI values. Our geometric midline estimation consistently demonstrated a midline shift towards the contralesional side indicative of swelling on Day 2 and a midline shift towards the ipsilesional side indicative of atrophy on Day 30 ( Figure 3B ). Conclusion: We have developed a validated, end-to-end automated pipeline for quantifying stroke injury in large, multi-site preclinical trials. This work delivers a scalable, objective, and reproducible framework as a shareable, open-source tool that enhances the rigor of preclinical research to help bridge the translational gap in stroke.

  PublisherDOI

• Behavioral deficits and exacerbated neural and hemodynamic odor responses during lifespan of a mouse model of late onset Alzheimer’s disease expressing humanized APOEε4 and Trem2*R47H

  Frontiers in Aging Neuroscience · 2026-02-16

  articleOpen access

  Alzheimer's disease (AD) poses a significant global health challenge, being the most prominent cause of dementia with prevalence increasing as the population ages. While the majority of AD cases are late-onset (LOAD), current animal models predominantly represent the more aggressive, faster progressing early-onset AD (EOAD), limiting their ability in assessing early biomarkers and gaining deeper understanding of LOAD progression. This study explores a promising translatable model, the APOE4.TREM2 mouse, which combines the APOE4 allele and the Trem2 p.R47H mutation, both linked to increased AD risk in the human population. We performed behavioral phenotyping and measured hemodynamics and neurovascular coupling in dorsal olfactory bulbs (dOB) during odor stimulation of the APOE4.TREM2 mouse line. Experimental evidence of olfactory dysfunction prior to clinical symptoms suggests the opportunity of utilizing smell testing and fMRI as tools for screening of AD, both for preclinical and clinical studies. Here we assess and confirm the translatability of the APOE4.TREM2 mouse LOAD model, reporting exacerbated anxiety, deficits in odor-based foraging and spatial memory, and exacerbated odor-evoked dOB neural and intrinsic responses, but stable neurovascular coupling, in an age-dependent manner.

  PublisherOA PDFDOI

• Methods for randomized, blinded, controlled evaluation of putative disease interventions in multilaboratory, preclinical assessment networks

  Lab Animal · 2026-02-18

  articleOpen access

  Science faces a reproducibility crisis, and public trust in science declines when large clinical trials, which had been qualified by promising preclinical studies, fail. While some clinical trial designs may have been inadequate, preclinical assessments of disease interventions might have lacked key elements of rigor such as treatment concealment, randomization, blinded outcomes, prespecified and adequate sample sizes, and models including comorbidities. Here, to demonstrate feasibility and practicality of enhanced rigor in preclinical assessment, we designed a six-laboratory network that implemented rigorous study elements, using acute ischemic stroke for demonstration. This network enrolled 2,615 rodents in 5 different models and implemented a multistage, multiarm statistical design that sequentially eliminated candidate interventions during interim analyses. The methods included centralized intervention packaging, randomization, data quality assessment and data archiving. Blinded analysis of 9,274 video-recorded behavioral tasks and 3,652 magnetic resonance images were evaluated. All tools and protocols are presented and could be adapted to preclinical assessment in other disease areas.

  PublisherOA PDFDOI

• Author Correction: Methods for randomized, blinded, controlled evaluation of putative disease interventions in multilaboratory, preclinical assessment networks

  Lab Animal · 2026-03-05

  articleOpen access
  PublisherOA PDFDOI

• Behavioral deficits and exacerbated hemodynamics during lifespan of a mouse model of late onset Alzheimer’s disease expressing humanized APOEε4 and Trem2*R47H

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-24

  preprintOpen access

  Abstract Alzheimer’s Disease (AD) poses a significant global health challenge, being the most prominent cause of dementia with prevalence increasing as the population ages. While the majority of AD cases are late-onset (LOAD), current animal models predominantly represent the more aggressive, faster progressing early-onset AD (EOAD), limiting their ability in assessing early biomarkers and gaining deeper understanding of LOAD progression. This study explores a promising translatable model, the APOE4.TREM2 mouse, which combines the APOE4 allele and the Trem2 p.R47H mutation, both linked to increased AD risk in the human population. We performed behavioral phenotyping and measured hemodynamics in dorsal olfactory bulbs (dOB) during odor stimulation of the APOE4.TREM2 mouse line. Experimental evidence of olfactory dysfunction prior to clinical symptoms suggests the opportunity of utilizing smell testing and fMRI as tools for screening of AD, both for preclinical and clinical studies. Here we assess and confirm the translatability of the APOE4.TREM2 mouse LOAD model, reporting exacerbated anxiety, deficits in odor-based foraging and spatial memory, and exacerbated odor-evoked dOB intrinsic responses in an age-dependent manner.

  PublisherOA PDFDOI

• [¹⁸F]SynVesT-1 PET Detects SV2A Changes in the Spinal Cord and Brain of Rats with Spinal Cord Injury

  Journal of Nuclear Medicine · 2025-07-17 · 5 citations

  articleOpen access

  Traumatic spinal cord injury (SCI) is a devastating neurologic condition lacking effective prognostic and treatment methods. PET imaging of synaptic vesicle glycoprotein 2A (SV2A) has been used in measuring synapse changes. We explore the feasibility of using [¹⁸F]SynVesT-1 PET to detect the synaptic changes in a rat model of SCI. <b>Methods:</b> [¹⁸F]SynVesT-1 PET scans were performed on rats with T7 moderate contusion injury (<i>n</i> = 9) and sham controls (<i>n</i> = 7) on day 1 and days 9–11 after injury. The simplified reference region method 2 was used to compute the distribution volume ratios (DVRs) for the spinal cord (SC) and the brain, with the cervical cord and brain stem as the reference region, respectively. The averaged SUV ratio 30–60 min after injection was calculated as an alternative outcome measure. Diffusion tensor imaging (DTI) was used to evaluate axonal changes on post mortem SCs. Western blotting, immunohistochemical staining, and immunofluorescence staining were used to confirm the imaging results. <b>Results:</b> [¹⁸F]SynVesT-1 showed the highest uptake in the cervical SC. Notably, the DVR at the injury epicenter in SCI rats showed a 61% decrease on day 1 and a 53% decrease on days 9–11, compared with sham controls. The changes in SUV ratio 30–60 min after injection were consistent with the changes in DVR. The fiber damage in the epicenter was identified by DTI, and the loss of SV2A was confirmed by immunohistochemical staining and Western blotting. Further, the amygdala, limbic insular cortex, and cerebellum were found to be significantly affected by the SCI on day 1 by PET. The DTI analysis revealed fiber damage in the internal capsule and somatosensory cortex. <b>Conclusion:</b> [¹⁸F]SynVesT-1 PET effectively identified synapse loss in the contusion SCI rat model. The quantification of synaptic density through SV2A PET presents a promising objective metric for evaluating novel therapeutics for SCI.

  PublisherOA PDFDOI

• Cysteine depletion triggers adipose tissue thermogenesis and weight loss

  Nature Metabolism · 2025-06-03 · 33 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• Development of Ultra-High Resolution in Vivo NMR Methods for Functional Molecular Physiology Studies in Mouse Brain

  NSF · $475k · 2001–2005

• NIH Grant R01DC003710

  NIH · $2.7M · 2008

• Assessing the Relationship between Cortical Oxidative Metabolism and Working Memory Deficits Under NMDA Receptor Blockade

  NIH · $404k · 2017–2019

• NIH Grant R01CA140102

  NIH · $1.6M · 2016

• NIH Grant R29NS037203

  NIH · $463k · 2004

Frequent coauthors

• Douglas L. Rothman

  Resonance Research (United States)

  263 shared

• Péter Hermán

  Yale University

  221 shared

• Basavaraju G. Sanganahalli

  Yale University

  187 shared

• Daniel Coman

  Yale University

  173 shared

• Hal Blumenfeld

  Yale University

  119 shared

• Robert G. Shulman

  Yale University

  83 shared

• Kevin L. Behar

  Yale University

  83 shared

• Ikuhiro Kida

  57 shared

Education

• Ph.D., Chemistry

  Yale University

  1995

Awards & honors

• Pilot Award, Yale-UCL Medical Technologies Collaborative: Im…
• Pilot Award, Juvenile Diabetes Research Foundation (2008)
• Niels Lassen Award, International Society for Cerebral Blood…
• 21st Century Science Initiative Grant: James S. McDonnell Fo…
• Melvin H. Knisely Award, International Society on Oxygen Tra…