The societal burden of misdiagnosed brain disorders and diseases is substantial. The Hyder lab is leading breakthroughs in quantitative and translational imaging technologies, based primarily on magnetic resonance methods, to visualize molecular processes of function and dysfunction at the laminar level.
A primary interest of the Hyder lab is to develop functional imaging techniques that relate neural activity to underlying laminar structure in health and disease. Emphasis is on fMRI, but other multi-modal fMRI methods in conjunction with MRS, electrophysiology, optical imaging, and PET are being sought for increased biomarker specificity.
Another active interest in the Hyder lab is molecular imaging with magnetic resonance technologies where several disciplines connect, from chemistry and physics to material science and physiology. A new molecular imaging method, pioneered in the Hyder lab called BIRDS, combines high MRI spatial resolution with high MRS molecular specificity. Highly precise molecular imaging with BIRDS is being sought.
Extensive Research Description
Specific areas of interest in functional imaging include (i) understanding the role of the extraordinarily high energy demands of ongoing and intrinsic activity within neural populations as potential for quantitative disease biomarker, (ii) advancing the spatiotemporal resolution of functional imaging to understand the relation of cellular metabolism in health and disease (e.g., healthy aging, Alzheimer’s disease, depression, epilepsy, schizophrenia), and (iii) developing advanced calibrated fMRI methods for using oxidative energy as an absolute index of neural activity, both with task and rest paradigms, across cortical and subcortical regions.
For molecular imaging we use a method called BIRDS, which we developed and quite unconventionally detects the paramagnetically-shifted and non-exchangeable protons from lanthanide (or transition) metal ion probes for high spatiotemporal resolution biosensing. Highly precise molecular imaging of temperature and pH is achievable with BIRDS. Current areas of relevance are (i) design of new molecular probes for BIRDS, (ii) early cancer detection and metastasis using absolute pH imaging, (iii) application of new probes for BIRDS as molecular targets for diseases (e.g., diabetes), and (iv) detection of tumor response to treatments (e.g., radiation, chemotherapy, heat).
Calibrated fMRI for basal metabolism – simulation studies to assess sensitivities required for fMRI and perfusion data to extract basal metabolism from calibrated fMRI data
Quantitative metabolic PET – analysis of whole brain PET data of glucose and oxidative metabolism in the human brain in relation to blood flow
Liposomal BIRDS – development and/or characterization of newly developed probes encapsulated inside liposomes for BIRDS
Dendrimeric BIRDS – development and/or characterization of newly developed macromolecular-based probes for BIRDS
- Bailey CJ, Sanganahalli BG, Herman P, Blumenfeld H, Gjedde A, Hyder F (2013) Analysis of time and space invariance of BOLD responses in the rat visual system. Cereb Cortex. 23:210-222
- Coman C, Trübel HK, Rycyna RE, Hyder F (2009) Brain temperature and pH measured by 1H chemical shift imaging of a thulium agent. NMR Biomed. 22:229-239
- Coman D, Trübel HK, Hyder F (2010) Brain temperature by Biosensor Imaging of Redundant Deviation in Shifts (BIRDS): Comparison between TmDOTP5- and TmDOTMA-. NMR Biomed. 23:277-285
- Coman D, Kiefer GE, Rothman DL, Sherry AD, Hyder F (2011) A lanthanide complex with dual biosensing properties: CEST (chemical exchange saturation transfer) and BIRDS (biosensor imaging of redundant deviation in shifts) with europium DOTA-tetraglycinate.
- Coman D, de Graaf RA, Rothman DL, Hyder F (2013) In vivo three-dimensional molecular imaging with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) at high spatiotemporal resolution. NMR Biomed. 26:1589-1595
- Duque A, George ED, Coman D, Bordner KA, Carlyle BC, Papademetris X, Hyder F, Simen AA (2012) Neuroanatomical changes in a mouse model of early life neglect. Brain Struct Funct. 217:459-472
- Herman P, Sanganahalli BG, Blumenfeld H, Hyder F (2009) Cerebral oxygen demand for short-lived and steady-state events. J Neurochem. 109 (Suppl 1):73-79
- Herman P, Sanganahalli BG, Hyder F, Eke A (2011) Fractal analysis of spontaneous fluctuations of the BOLD signal in rat brain. NeuroImage. 58:1060-1069
- Herman P, Sanganahalli BG, Blumenfeld H, Rothman DL, Hyder F (2013) Quantitative basis for neuroimaging of cortical laminae with calibrated fMRI. Proc Natl Acad Sci USA. 110:15115-15120
- Herzog RI, Jiang L, Herman P, Zhao C, Sanganahalli BG, Mason GF, Hyder F, Rothman DL, Sherwin RS, Behar KL (2013) Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia. J Clin Invest. 123:1988-1998
- Hyder F, Rothman DL (2010) Neuronal correlate of global BOLD signal fluctuations at rest: Err on the side of baseline. Proc Natl Acad Sci USA. 107:10773-10774
- Hyder F, Rothman DL (2011) Evidence for the importance of measuring total brain activity in neuroimaging. Proc Natl Acad Sci USA. 108:5475-5476
- Hyder F, Rothman DL (2012) Quantitative fMRI and oxidative neuroenergetics. NeuroImage. 62:985-994
- Hyder F, Rothman DL, Bennett MW (2013) Cortical energy demands of signaling and non-signaling components are conserved across mammalian species and activity levels. Proc Natl Acad Sci USA. 110:3549-3554
- Hyder F, Fulbright RK, Shulman RG, Rothman DL (2013) Glutamatergic function in the resting awake human brain is supported by uniformly high oxidative energy. J Cereb Blood Flow Metab. 33:339-347
- Lacar B, Herman P, Hartman N, Hyder F, Bordey A (2012) S phase entry of neural progenitor cells correlates with increased blood flow in the adolescent subventricular zone. PLoS One. 7(2):e31960
- Lacar B, Herman P, Platel JC, Kubera C, Hyder F, Bordey A (2012) Neural progenitor cells regulate capillary blood flow in the postnatal subventricular zone. J Neurosci. (in press)
- Mishra AM, Ellens DJ, Schridde U, Motelow JE, Purcaro MJ, DeSalva MN, Enev M, Sanganahalli BG, Hyder F, Blumenfeld (2011) Where fMRI and electrophysiology agree to disagree: corticothalamic and striatal activity patterns in the WAG/Rij rat. J Neurosci. 31
- Mishra AM, Bai X, Motelow JE, DeSalvo M, Danielson N, Sanganahalli BG, Hyder F, Blumenfeld H (2013) Increased resting functional connectivity in spike-wave epilepsy in WAG/Rij rats. Epilepsia. 54:1214-1222
- Sanganahalli BG, Herman P, Blumenfeld H, Hyder F (2009) Oxidative neuroenergetics in event-related paradigms. J Neurosci. 29:1707-1718
- Sanganahalli BG, Herman P, Hyder F, Kannurpatti SS (2013) Mitochondrial modulation of spontaneous neocortical activity: Implications for resting state fMRI of neuropathology. PLoS ONE. 8(5):e63317
- Sanganahalli BG, Herman P, Hyder F, Kannurpatti SS (2013) Mitochondrial calcium uptake capacity modulates neocortical excitability. J Cereb Blood Flow Metab. 33:1115-1126
- Sanganahalli BG, Herman P, Behar KL, Blumenfeld H, Rothman DL, Hyder F (2013) Functional MRI and neural responses in a rat model of Alzheimer's disease. NeuroImage. 79:404-411
- Scafidi J, Roncal M, Jablonska B, Coman D, Huang Y, Hammond T, Szigeti-Buck K, Hyder F, Horvath TL, McCarter Jr. RJ, Gallo V (2014) Intranasal epidermal growth factor treatment rescues neonatal brain injury. Nature. (in press)
- van Luijtelaar G, Mishra AM, Edelbroek P, Coman D, Frankenmolen N, Schaapsmeerders P, Covolato G, Danielson N, Niermann H, Janeczko K, Kiemeneij A, Burinov J, Bashyal C, Coquillette M, Luttjohann A, Hyder F, Blumenfeld H, van Rijn CM (2013) Anti-epileptog