About

Ravi Prakash Reddy Nanga, Ph.D., R.Ph., is a Research Associate Professor of Radiology at the University of Pennsylvania's Perelman School of Medicine. His research focuses on the study of brain metabolites in vivo in humans, particularly in disease states such as epilepsy, schizophrenia, and in acute drug studies, utilizing MR spectroscopy and CEST MRI techniques. He has led several preclinical and clinical research projects involving spectroscopic and CEST acquisitions and has recently contributed to the development of down-field MR spectroscopy. His goal is to extend his expertise to study metabolism for early detection and therapeutic monitoring of neurodegenerative diseases and neurological disorders.

Research topics

• Biochemistry
• Biology
• Artificial Intelligence
• Physics
• Computer Science
• Chemistry
• Nuclear magnetic resonance
• Neuroscience

Selected publications

• Pharmacokinetic effects of a single dose nutritional ketone ester supplement on brain glucose and ketone metabolism in alcohol use disorder

  Psychiatry Research Neuroimaging · 2026-01-29 · 1 citations

  articleOpen access

  Acute alcohol use reduces brain glucose metabolism while increasing uptake of acetate, a byproduct of alcohol. This metabolic shift persists in individuals with alcohol use disorder (AUD) and may offer a treatment target. Recent studies show that ketone therapies can lessen alcohol withdrawal and cravings. In this study, we tested whether a single dose of a ketone ester (KE) supplement affects brain energy use and alcohol craving. Ten participants (five with AUD, five healthy controls) received two FDG-PET brain scans-one after taking 395 mg/kg KE and one at baseline-in a randomized order. Additionally, five AUD participants underwent magnetic resonance spectroscopy to measure cingulate β-hydroxybutyrate (BHB). KE lowered blood glucose and increased BHB in both groups. Brain scans revealed a 17% reduction in glucose metabolism, especially in the frontal, occipital, and cingulate cortices, as well as the hippocampus, amygdala, and insula. No major differences were observed between AUD and control groups. KE significantly reduced alcohol craving in AUD participants and tripled cingulate BHB levels. These findings suggest that a single KE dose can rapidly shift brain energy use from glucose to ketones, and may help reduce cravings in AUD, supporting its potential as a therapeutic approach.

  PublisherDOI

• An imaging biomarker to detect non-glucogenic shift in brain energy metabolism in Alzheimer’s disease

  Journal of Translational Medicine · 2026-05-20

  articleOpen access

  Cerebral glucose hypometabolism in Alzheimer’s disease (AD) leads to enhanced metabolism of fatty acids (FAs) and branched-chain amino acids (BCAAs) as a compensatory mechanism. While there have been some 13C labeled studies investigating the metabolism of FAs and BCCAs, their clinical translation is challenging. In this study, we investigated the potential of measuring neurometabolic perturbations through macromolecular signal at 0.9 ppm (MM09) in proton magnetic resonance (1H MR) spectrum. This signal represents a composite macromolecular signal with contributions from lipids and BCAA associated methyl resonances and may be sensitive to metabolic alterations occurring during glucose hypometabolism in AD. MM09 levels were measured from localized 1H MR spectra in the hippocampus and thalamus/hypothalamus of male and female APPNL−F/NL−F (AD) mice. In addition, the levels of glutamate in these regions were also recorded as it is known to be reduced under glucose hypometabolism in AD. We further studied the metabolic association of MM09 with glutamate in Pearson correlation plots. To find the statistical significance of difference two-way ANOVA analysis with post-hoc Tukey HSD tests were used. Male AD mice exhibited significantly reduced MM09 (15.42 ± 1.32 vs. 16.93 ± 1.15 mM; p = 0.008) and glutamate levels (15.27 ± 1.65 vs. 17.24 ± 1.21 mM; p = 0.004) in the hippocampus. Female AD mice did not show any changes in glutamate or MM09 levels. MM09 also showed a strong positive correlation with glutamate (R = 0.74; p < 0.0001). The observed reductions in MM09 and glutamate in male AD mice are consistent with neurometabolic alterations associated with impaired glucose metabolism, whereas the absence of such changes in female AD mice may reflect sex-specific metabolic resilience. The strong association between MM09 and glutamate suggests that MM09 may capture neurochemical changes linked to metabolic adaptations in AD. Because the MM09 resonance occurs in a relatively uncrowded region of the 1H MR spectrum, it may represent a promising spectroscopic marker for investigating metabolic shifts in AD and warrants further evaluation in clinical studies.

  PublisherDOI

• Contrast-induced changes in chemical exchange saturation transfer MRI differentiate tumor progression from pseudoprogression

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-05

  articleOpen access

  Tumor pseudo-progression (PsP) refers to an initial increase in tumor size or the appearance of new lesions. These pseudo-progressive lesions are predominantly composed of infiltrative inflammatory cells, such as macrophages. This phenomenon commonly occurs in patients undergoing radiation therapy or immunotherapy and typically indicates a positive treatment response. However, it often leads to premature treatment cessation due to misinterpretation as disease progression. Non-invasive imaging biomarkers capable of distinguishing pseudo-progression from true progression would greatly aid in treatment decision-making. In our preliminary study, we explored the potential of gadoterate meglumine (Gd-DOTA, a macrocyclic Gd-contrast) in combination with amine chemical-exchange saturation transfer (amine-CEST) imaging to differentiate tumor from radiation necrosis by assessing Gd-DOTA uptake by infiltrating immune cells, such as macrophages. To evaluate whether amine-CEST, in combination with Gd-DOTA, can differentiate macrophages from cancer cells, we incubated them with Gd-DOTA for 30 minutes. Subsequently, the cells were processed, and amine-CEST imaging was performed on a 9.4 Tesla preclinical scanner. Upon treatment with Gd-DOTA, we did not observe a significant change in amine-CEST contrast in F98 cells compared with untreated cells, whereas treated macrophages exhibited a marked decrease (~40%) in amine-CEST signal compared with untreated macrophages. This reduction in signal was attributed to the uptake of Gd-DOTA by macrophages, which notably shortened water T1 relaxation, thereby quenching the amine-CEST signal. Conversely, cancer cells showed no appreciable change in the amine-CEST signal, indicating no Gd-DOTA uptake. Furthermore, to validate that T1 shortening influences amine-CEST signal, cancer cells were also treated with manganese chloride (MnCl2) for 30 minutes. The uptake of MnCl2 by cancer cells similarly induced T1 shortening, as observed in macrophages, resulting in a decrease in the amine-CEST signal from these cells. Next, we performed the amin-CEST imaging on F98 tumor-bearing rats and radiation necrotic rats. Post-injection with Gd-DOTA showed no appreciable change in the amine-CEST contrast in the tumor-bearing rat, whereas a significant decrease in contrast was observed in the radiation necrotic rat. This further demonstrates that no change in the amine-CEST contrast in tumor-bearing rats is due to cancer cells failing to take up Gd-DOTA. The decrease in amine-CEST contrast in radiation-treated rats reflects the uptake of Gd-DOTA by macrophages infiltrating the radiation-necrotic regions. This straightforward imaging approach holds promise for clinical translation. It offers a novel method for characterizing pseudo-progressive lesions and monitoring diverse treatment responses in cancer patients using standard clinical scanners.

  PublisherOA PDFDOI

• In vivo imaging of glutamate uncovers the neuroprotective effects of nicotinamide riboside on excitotoxicity in an Alzheimer’s mouse model

  Alzheimer s Research & Therapy · 2026-01-30

  articleOpen access

  Nicotinamide adenine dinucleotide (NAD+) precursors, such as nicotinamide riboside (NR), have gained interest as potential therapeutics for alleviating Alzheimer’s disease (AD) pathology. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can provide insights into the effects of NR on AD by virtue of its sensitivity to monitoring the metabolic status of tissue in vivo. This study used glutamate-weighted CEST (GluCEST) MRI to monitor glutamate-associated metabolic changes following NR treatment in the 5xFAD mouse model of AD. Drinking water was supplemented with NR or provided as is to animals over the course of expected disease progression prior to imaging experiments. Following imaging, an immunohistochemical assay to monitor the expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba1) was performed to assess the extent of neuroinflammatory glial responses. A two-way ANCOVA with interaction was performed for statistical analysis of both CEST and IHC data. Results from GluCEST revealed significantly higher glutamate levels in the hippocampal dentate gyrus of AD mice compared to WT, with a significant reduction following treatment. GFAP staining mirrored this trend, implicating reactive astrogliosis as a mechanism for elevated glutamate. Similar patterns were observed in the cerebral peduncles, a white matter bundle, in which GFAP and Iba1 supported GluCEST findings and suggested neuroinflammation in axonal tracts. Our findings are in concordance with studies reporting elevated glutamate associated with reactive gliosis and morphological changes disrupting glutamate imbalance. Interestingly, NR restores glutamate homeostasis and alleviates neuroinflammatory processes, thus rescuing tissue from excitotoxic insults. Overall, this study demonstrates the potential of NR to mitigate glutamate-driven excitotoxicity in AD pathology, and highlights GluCEST as a sensitive in vivo, clinically translatable biomarker for neuroinflammation and excitotoxicity.

  PublisherDOI

• Magnetic Resonance Imaging for Improved Brain Tumor Detection

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-11 · 1 citations

  preprintOpen access

  Abstract Precise demarcation of brain tumor boundaries is critical for optimizing treatment strategies and improving patient outcomes. In vivo characterization of tumor using PET/CT and MRI is clinical standard. PET/CT highlights the metabolic aspects of the tumor, while MRI provides information on functional, metabolic and structural changes. Even with technological advancements in both PET/CT and MRI, a method that can precisely delineate infiltrative tumor boundaries from normal-appearing brain regions (NABR) in vivo is still lacking. To address this limitation, we explored a relatively new MR imaging method, the Nuclear Overhauser Effect Magnetization Transfer Ratio (NOE MTR ), in conjunction with a gadolinium-based contrast agent (Gd-DOTA), to precisely delineate the tumor boundaries in a rat model of infiltrative gliosarcoma. NOE MTR imaging was performed in the rat model (n=5) before and after Gd-DOTA administration. The post-Gd-DOTA NOE MTR map was subtracted from the pre-Gd-DOTA map and compared with contrast-enhanced T 1 -weighted images and immuno-histological findings. The resulting NOE MTR difference map clearly highlighted both the tumor core and infiltrative boundaries, which was not discernible on the post-contrast T 1 -weighted images. The extended tumor boundaries observed on the NOE MTR difference map corroborated with the IHC image, which confirmed the presence of infiltrative tumor cells and macrophages in these regions. Guided by the NOE MTR difference map, regions of interest (ROI) were drawn to quantify NOE MTR signal changes in the tumor core, tumor boundaries, and NABR post-Gd-DOTA. Tumor core showed a significant ∼43% reduction in NOE MTR signal (plJ=lJ0.003), while the tumor periphery exhibited a moderate reduction of ∼10%, (plJ=lJ0.045). No appreciable change in was observed in the NABR (plJ=lJ0.371). In contrast, the post contrast T 1 -weighted signal changes in tumor core, tumor periphery and NABR were, 33.32% (p = 0.092), 3.8% (p = 0.478), and 8.7% (p = 0.464) respectively. These findings suggest that NOE MTR imaging provides enhanced tumor contrast, particularly at the infiltrative tumor margins, where conventional contrast enhanced T 1 -weighted MRI may underestimate tumor extent. Histological validation confirmed the presence of infiltrative tumor cells and macrophages in the tumor periphery, as highlighted by the NOE MTR difference map. Overall, NOE MTR imaging, in combination with Gd-DOTA administration, demonstrates superior delineation of brain tumor boundaries compared to conventional MRI. As NOE MTR imaging is a fast acquisition scan (under 10 minutes) and performed on standard 3 Tesla, it can be easily integrated into clinical protocols. By improving visualization of tumor infiltration and distinguishing tumor regions from NABR, NOE MTR imaging holds promise for advancing neuro-oncological diagnostics and treatment planning.

  PublisherOA PDFDOI

• In Vivo Brain B₁⁺ Inhomogeneity Correction and NOE Image Enhancement at 7 T via Flexible Metasurfaces

  NMR in Biomedicine · 2025-04-02 · 3 citations

  articleOpen access

  ABSTRACT 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 radiofrequency (RF) wavelengths at ultra‐high fields. 2D periodic unit cell metasurfaces have been a promising approach for providing improvements in anatomical imaging but have not yet been evaluated in chemical exchange saturation transfer (CEST)‐based sequences. Here, we report the use of metasurfaces for enhancement of NOE imaging as well as for improvement of Lorentzian line fitting of full Z‐spectrum data. 3D NOE image data, B 1 + maps, and B 0 maps were acquired on five healthy volunteers using a 7 T MRI system with and without metasurfaces positioned near the temporal lobes. A frequency offset range of −5 to +5 ppm with additional separate acquisitions of ±20 and ±100 ppm offset images. A five‐pool Lorentzian line fitting model was employed to fit and quantitatively compared magnetization transfer (MT), amide proton transfer (APT), amine, and relayed NOE (rNOE) metabolite pools. NOE MTR ‐weighted contrast maps were also calculated via Z‐spectrum asymmetry analysis. The metasurfaces globally enhanced the transmit efficiency within the imaging slab by approximately 9.6% and reduced B 1 + inhomogeneity by approximately 16.6% and increased transmit efficiency by 55.8% in the temporal lobes. Amplitude fit maps showed decreases in contrast magnitude ranging from 1 to 16% and changes in image uniformity ranging from a 4.3 decrease to a 34.7% increase, while NOE MTR ‐weighted contrast maps demonstrated similar changes. The results presented here demonstrate that metasurfaces can enhance CEST‐based techniques complementing previously reported benefits in anatomical imaging.

  PublisherOA PDFDOI

• NOE Imaging of Multiple Sclerosis Subjects at 7T Detects Diffuse Contrast Changes

  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: While standard to the diagnosis of multiple sclerosis (MS), conventional structural MRI cannot provide detailed information on changes in lipid metabolism. Goal(s): To utilize NOE imaging to investigate changes between MS and healthy control subjects. Approach: NOE imaging was performed on 15 MS and 10 healthy subjects in conjunction with a multi-pool Lorentzian line fitting model to produce several contrasts including MT, APT, amine, and rNOE. Results: Statistically significant contrast decreases were observed in both the amine (15.3% in NAWM) and rNOE (11.4% in NAWM and 10.6% in NAGM) pools. Impact: This 7T NOE imaging method for patients with MS can provide complementary lipid metabolic information to standard structural imaging and can yield improved diagnostic outcomes for this patient population.

  PublisherDOI

• Effects of nicotinamide riboside supplementation on glucose metabolism and lipid homeostasis in healthy mice

  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: The rising popularity of NAD+ precursors to alleviate metabolic stress in aging necessitates a close monitoring of tissue metabolic status. Goal(s): FINUTE and 2H-MRS are used monitor lipid homeostasis and glucose metabolism in the brains of healthy mice following supplementation of nicotinamide riboside (NR), a widely used NAD+ precursor. Approach: Mice administered saline or NR intraperitoneally for one week are imaged to assess lipid integrity. 2H-MRS is performed following administration of labeled glucose to monitor downstream metabolite labeling. Results: Mice administered NR show increased lipid integrity and improved glucose metabolism, determined through increased labeling of Glx (TCA) and lower labeling of lactate (glycolysis). Impact: Nicotinamide riboside has potential in improving cerebral glucose metabolism and lipid integrity as assessed by lipid-sensitive MRI and 2H-MR spectroscopy, necessitating further exploration of NR and other NAD+ precursors both clinically and in aging-related diseases using these methods.

  PublisherDOI

• Characterizing Spatial Associations Between <scp>GluCEST MRI</scp> and Neurotransmitter Receptor Density in the Human Cortex

  Human Brain Mapping · 2025-12-15 · 1 citations

  articleOpen access

  ABSTRACT Glutamate‐weighted Chemical Exchange Saturation Transfer (GluCEST) captures in vivo glutamate (Glu) levels with high spatial resolution and has been used to assess glutamatergic function in healthy and clinical populations. While GluCEST is well‐validated against proton magnetic resonance spectroscopy ( 1 H‐MRS), its correspondence with local expression of glutamatergic neurotransmitter receptors remains unclear. Recent initiatives, such as Neuromaps, have collated positron emission tomography (PET) data into curated, publicly available databases, providing a novel opportunity to establish convergence in the regional distribution of GluCEST and normative receptor density maps. Here, we examine the spatial correspondence between GluCEST signal and PET‐based cortical receptor density levels of N‐methyl‐D‐aspartate (NMDA), metabotropic glutamate receptor 5 (mGluR5), and gamma‐aminobutyric acid A (GABA A ). A cohort of 86 participants (age: 22.7 years [3.7 years], 45% female) included 34 individuals with no psychiatric history, 31 participants with significant sub‐threshold psychosis symptoms, and 21 participants with first‐episode psychosis. All participants underwent 7T GluCEST imaging. Data were processed using in‐house and field‐standard pipelines. Mean receptor density levels were computed using the Neuromaps PET receptor density data. GluCEST and Neuromaps data were parcellated using the Cammoun 500 atlas. Pearson correlations assessed the correspondence between GluCEST signal and PET‐based receptor density, and spin tests were used for empirical significance testing of the spatial correlations across all parcels. Sensitivity analyses examined the effect of age, sex, and diagnosis and other covariates. Exploratory analyses assessed regional variability across cytoarchitecturally defined von Economo regions and overall trends with gene expression. Analyses were performed in Python and R. GluCEST signal converged with the regional distribution of both NMDA ( r = 0.23, p spin = 0.039) and GABA A ( r = 0.35, p spin = 0.004). There was no significant effect for mGluR5 ( r = 0.09, p spin &gt; 0.05). Exploratory analyses indicated that cytoarchitecturally defined von Economo regions showed variable GluCEST‐receptor association patterns across the cortex and that gene expression patterns generally correspond with receptor density findings. Our findings reveal a positive spatial association between GluCEST signal in a transdiagnostic cohort and atlas‐based PET‐derived cortical receptor density of NMDA and GABA A , and a nominal positive association with mGluR5. The association between GluCEST and NMDA suggests that regions with dense ionotropic Glu receptors exhibit higher Glu levels, while the coupling between GluCEST and GABA A may reflect tight regulation of excitation‐inhibition balance. Regional differences in these associations point to the potential influence of local cytoarchitectural specialization on Glu‐receptor dynamics. These results advance our understanding of the neurobiological basis of GluCEST and highlight its potential utility as a non‐invasive tool for probing receptor‐mediated glutamatergic neurotransmission.

  PublisherOA PDFDOI

• Measurement of tryptophan relaxation times in human brain using downfield 1H MRS at 7 T

  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: Determine the tryptophan (TRP) relaxation rates from human brain 1H downfield spectrum in vivo. Goal(s): To estimate the T1 and T2 of TRP in healthy human brains at 7 T Approach: We determined TRP relaxation times using a spectrally- and slice-selective downfield MRS sequence. Results: The mean T1 and T2 estimates of TRP from in vivo human brain were 74.5±12.5ms (n=6) and 19.3±3.5ms (n=8), respectively. Impact: Reliable in vivo brain TRP relaxation measures in normal subjects could help establish reference values and also aid in utilizing it as a novel non-invasive in vivo biomarker for various aging-related and neuropsychiatric disorders.

  PublisherDOI

Frequent coauthors

• Ravinder Reddy

  83 shared

• Hari Hariharan

  University of Pennsylvania

  33 shared

• Ayyalusamy Ramamoorthy

  National High Magnetic Field Laboratory

  28 shared

• John A. Detre

  University of Pennsylvania

  22 shared

• Mark A. Elliott

  University of Pennsylvania

  20 shared

• Neil Wilson

  University of Pennsylvania

  19 shared

• Walter R. Witschey

  19 shared

• Mohammad Haris

  19 shared

Education

• PhD, Chemistry

  University of Michigan

  2011