About

Daniel Coman, PhD, is an Associate Professor of Radiology and Biomedical Imaging and of Biomedical Engineering at Yale School of Medicine. His research focuses on the development of molecular imaging methods to reveal physiological and chemical alterations underlying disease in preclinical models and to exploit these findings in clinical applications. He utilizes advanced Magnetic Resonance (MR) techniques, including multi-nuclear MR Spectroscopy and multi-modal MR Imaging, to conduct in vivo biomedical imaging research on both pre-clinical and clinical scanners. His primary research interest is in developing new MR imaging biomarkers for cancer, aiming to better understand resistance mechanisms and design new therapies. Notably, he developed an ultrafast MR Spectroscopic Imaging technique called Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) for mapping the acidic microenvironment of cancer. His work encompasses exploring tumor microenvironments, endothelial dysfunction, and the use of high-resolution thermal imaging to delineate effects of cancer-induced aerobic glycolysis and endothelial dysfunction. Dr. Coman's research also includes investigating brain and liver neoplasms, molecular imaging, and the development of biomarkers to improve cancer diagnosis and treatment.

Research topics

• Medicine
• Internal medicine
• Biology
• Cancer research
• Materials science
• Pathology
• Chemistry
• Pharmacology
• Physiology
• Endocrinology
• Nanotechnology

Selected publications

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

  Neuro-Oncology Advances · 2026-01-01

  articleOpen access1st authorCorresponding

  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

• Cover Image

  NMR in Biomedicine · 2025-01-12

  paratextOpen access
  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

• Multimodal imaging reveals gliomas are cooler than normal tissue

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  article1st authorCorresponding

  Motivation: CBF-CMRO2 uncoupling in tumors suggests that the tumor temperature might be different than normal brain temperature. Goal(s): To determine if a temperature gradient exists between tumor and normal brain tissue. Approach: We measured CMRO2, CMRgly, and CBF in rat brains bearing 9L tumors, and calculated the brain temperature distribution using Pennes bioheat equation. We measured the temperature distribution in 9L, RG2, U87 and U251 gliomas using BIRDS with TmDOTP5- and we confirmed these measurements by 1H-MRS using water-NAA and by BIRDS with TmDOTMA-. Results: Our measurements indicate that the tumor temperature is lower by ~10C compared to normal brain temperature. Impact: Temperature regulates the immune response, and thermal- and immuno-therapy might be combined for improved outcome. While temperature is rarely included into discussions related to tumor microenvironment, our results potentially impact future therapeutic directions because cooler conditions enhance tumor growth.

  PublisherDOI

• Cysteine depletion triggers adipose tissue thermogenesis and weight loss

  Nature Metabolism · 2025-06-03 · 33 citations

  articleOpen access
  PublisherOA PDFDOI

• Liver pH imaging for diagnosis and prognosis

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  articleSenior author

  Motivation: Extracellular acidosis is a unique feature of the tumor microenvironment (TME). The low pHe can reduce the cytotoxic activity of immune T-cells and enhance the tumor-promoting phenotype of macrophages, supporting an immunosuppressive TME. Goal(s): To accurately correlate pHe with density of immune cells, imaging pHe at submillimeter resolution is necessary Approach: pHe imaging at submillimeter resolution was achieved using a special k-space sampling strategy, called REduced Spherical Encoding with GAussian Weighting (RESEGAW) Results: We demonstrate the feasibility of pHe imaging with RESEGAW at isotropic 0.6mm resolution in a mouse liver tumor model. The pHe with RESEGAW was validated using 31P MRSI with 3-APP. Impact: This study validates high-resolution pHe imaging in mouse liver tumors using RESEGAW, enabling precise, noninvasive metabolic characterization. By mapping pHe at 0.6 mm isotropic resolution, it advances understanding of TME acidity and immune dynamics, potentially guiding liver cancer therapies.

  PublisherDOI

• Intranasal Leukemia Inhibitory Factor as a late-stage treatment for delayed white matter damage in concussive head injury

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-07

  preprintOpen access

  Leukemia Inhibitory Factor (LIF) is an injury-induced cytokine that peaks 48 hours after a traumatic brain injury (TBI). Juvenile LIF haplodeficient mice exhibit desynchronized glial responses, increased neurodegeneration, decreased axonal conductivity and behavioral deficits after a concussive head injury. Given the necessity of LIF during the acute recovery phase after injury, we hypothesized that intranasal LIF (IN-LIF) treatment would prevent neurodegeneration when administered during the chronic recovery period from a mild TBI (mTBI). Young adult male CD1 mice were subjected to a midline, closed-head frontal cortex injury using a flat metal impactor with a 3mm tip to induce a mTBI. In the 6-8 weeks post-mTBI, known to precede axonal atrophy in this mTBI model, two doses of 40 ng and 100 ng of LIF were administered twice daily, 5 days/week for two consecutive weeks. Sensorimotor functions were assessed at 4 and 8 weeks post mTBI, followed by ex-vivo brain magnetic resonance imaging at 9.4T and histopathology. mTBI mice showed sensorimotor deficits at 4 weeks, which worsened by 8 weeks post-injury. IN-LIF treatment prevented the progressive sensorimotor loss seen in the vehicle-treated controls. Increased mean diffusivity and decreased fractional anisotropy were observed in the corpus callosum and prefrontal cortex of mTBI brains. In a dose-dependent manner, IN-LIF prevented the mTBI-induced mean diffusivity increase and fractional anisotropy decrease. Histologically, there was significantly less astrogliosis, microgliosis and axonal injury in the IN-LIF treated mice vs. controls. These results support the therapeutic potential of IN-LIF to reduce delayed neurodegeneration and improve neurological outcomes after mTBIs.

  PublisherOA PDFDOI

• Sorafenib Alters Interstitial Proton and Sodium Levels in the Tumor Microenvironment: A ¹H/²³Na Spectroscopic Imaging Study

  NMR in Biomedicine · 2025-01-07 · 1 citations

  article

  ABSTRACT Cellular metabolism is inextricably linked to transmembrane levels of proton (H + ), sodium (Na + ), and potassium (K + ) ions. Although reduced sodium‐potassium pump (Na + ‐K + ATPase) activity in tumors directly disturbs transmembrane Na + and K + levels, this dysfunction is a result of upregulated aerobic glycolysis generating excessive cytosolic H + (and lactate) which are extruded to acidify the interstitial space. These oncogene‐directed metabolic changes, affecting intracellular Na + and H + , can be further exacerbated by upregulation of ion exchangers/transporters. As Na + /H + imbalances impact tumor invasion, chromosomal rearrangements, proliferation rate, angiogenesis, and immune function, measuring interstitial H + (H + o ) or pH (pH o ) and interstitial Na + (Na + o ) could provide unique insights into cancer hallmarks. We obtained proton ( 1 H) and sodium ( 23 Na) magnetic resonance spectroscopic imaging (MRSI) data to map pH o and Na + o in a human‐derived glioblastoma model (U87) in vivo with sorafenib (protein kinase inhibitor) treatment and a placebo. In U87 tumors, sorafenib slowed tumor growth compared to placebo and restored transmembrane H + and Na + levels. Placebo tumors maintained an interstitial space that was less salty and more acidic, similar to naive U87 tumors, implying a proliferative state. However, sorafenib‐treated tumors had interstitial space that became more salty and less acidic, comparable to normal tissue. Importantly, these interstitial ionic changes occurred prior to tumor growth changes. These results imply that glioblastoma therapies, which may perturb transmembrane ions by different mechanisms (e.g., ion pumping, exchange, and/or transport), can be tracked by merging 1 H with 23 Na MRSI to measure treatment effectiveness.

  PublisherDOI

• Leukemia Inhibitory Factor as a Late-Stage Treatment for Delayed White Matter Loss in Concussive Head Injury

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Transition metal based phosphonated macrocyclics for pH biosensing

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  article

  Motivation: Lanthanide ion-based first-generation MRI contrast agents (like GBCAs) enhance detection of pathologic structures by shortening water proton relaxation but provide no physiological information. Goal(s): Develop second-generation MRI agents that enhance relaxivity-based detection and selectively map physiological parameters through hyperfine shifted proton resonances. Approach: Designing and synthesizing novel paramagnetic MR agents with Co(II) and Ni(II) ions coordinated phosphonated macrocyclic ligands for pH biosensing, aiding early detection of tumors, ensuring clinical translation. Results: We synthesized Co(II) and Ni(II) coordinated phosphonated macrocyclic complexes [M(II)L]. Co(II)Lx- has 6.5 ppm/pH sensitivity, 1.5-fold larger than TmDOTP5-, while Ni(II)Lx- has 2.7 ppm/pH, comparable to TmDOTP5-. Impact: The Co(II)Lx- exhibited highest pH sensitivity among all reported biosensors. These biocompatible pH sensors are under evaluation for in vivo pH mapping, aiming to enable early cancer diagnosis and holding strong potential for clinical translation.

  PublisherDOI

Frequent coauthors

• Fahmeed Hyder

  Yale University

  173 shared

• Douglas L. Rothman

  Resonance Research (United States)

  41 shared

• Yuegao Huang

  37 shared

• Basavaraju G. Sanganahalli

  Yale University

  37 shared

• Péter Hermán

  Yale University

  30 shared

• Sandeep K. Mishra

  26 shared

• John J. Walsh

  Griffith University

  24 shared

• Samuel Maritim

  Resonance Research (United States)

  23 shared