- Assistant Professor: 2005-present: Department of Neurology,
- Research Biologist: May, 2000-present, VA Medical Center, Baltimore, Baltimore, MD
- Postdoctoral Fellow: 1997-2000, University of Miami School of Medicine, Miami FL - Stephen D. Roper, Ph.D.
- Graduate Research Assistant (thesis research): 1993-1997, University of Maryland School of Medicine, Baltimore MD - Daniel Weinreich, Ph.D.
- Graduate Research Assistant: 1992-1993, University of Maryland School of Medicine, Baltimore MD - Jay Yang, M.D., Ph.D.
- Research Technician: 1986-1989, Duke University Eye Center, Durham NC - Alan Proia, M.D., Ph.D.
- Undergraduate: BS, Chemistry with biological specialization, Duke University, Durham NC, 1985
My lab is primarily focused on neurodegeneration and neuroprotection, mainly focusing on Parkinson's disease. We have two primary areas of interest:
- improving neurosurgical outcomes for deep brain stimulation electrode placement and other neurosurgical procedures
- developing new neuroprotective strategies using our novel in vitro organotypic nigrostriatal coculture system. [under construction, but see references]
We have developed an ex vivo imaging method to create a detailed human brain map with resolution that's at least an order of magnitude better than MRI-derived maps. In a parallel project, we are developing a optical coherence tomographic (OCT) probe that can detect the orientation of fiber tracts and the pulsation of blood vessels. OCT-guided DBS with a highly precise, detailed brain map will make selective targeting of either neurons or axonal projections common place, and OCT-guided DBS with the ability to see and avoid blood vessels will eliminate the risk of peri-operative intracranial hemorrhages. Combining the virtues of both projects will revolutionize the DBS targeting.
Neurosurgical Guidance and Blood Vessel Detection:
Neurosurgical procedures are becoming an increasingly important therapeutic tool. The use of deep brain stimulating (DBS) electrodes for the treatment of Parkinson's disease is increasing and the use of DBS electrodes to treat disorders ranging from depression to obsessive-compulsive disorder to obesity to epilepsy is on the horizon. While success rates have been good, the risk of hemorrhage during surgery is still a dangerous and sometimes fatal complication of all neurosurgical procedures. Our newly developed forward scanning optical coherence tomography (OCT) probe can detect blood vessels along the surgical track ahead of the probe. Our OCT system also allows for real time monitoring of trajectory and targeting to improve electrode placement.
To address these issues we have taken a multipronged approach:
- We have developed a catheter-based optical coherence tomography imaging system to provide real-time optical feedback from the tip of the probe as it is advanced through the brain.
- We are mapping blood vessels in the brain to help identify the location of at risk vessels.
- We are also developing a high-resolution three-dimensional atlas of the human basal ganglia.
- We have also constructed a novel lighting system that allows us to use optical anisotropy to identify individual tracts in the basal ganglia.
Our current status in each of these areas is shown below.
Blood Vessel Mapping and Detection
Differentiating veins and arteries using gated laser Doppler audio signal
(Work-in-progress in collaboration with Dr. Cha-Min Tang, University of Maryland School of Medicine, and Dr. Yu Chen and Chia-Pin Liang, University of Maryland College Park)
The novel gated laser Doppler imaging probe we have developed allows us to detect blood vessels in front of the probe by audio feedback. Arteries and veins each have their own distinctive audio signatures. These signals were recorded from rat femoral vessels.
3-D display of blood vessels relevant in DBS procedures:
(Work-in-progress in collaboration with Dr. Cha-Min Tang, University of Maryland School of Medicine)
In these videos, the subthalamic nucleus is segmented out in yellow with the rest of the basal ganglia to the left and the thalamus above and to the right.
We are currently working to improve the resolution of the display and to distinguish arteries from veins.
Blood vessel detection of forward imaging OCT needle probe:
(Work-in-progress in collaboration with Dr. Cha-Min Tang, University of Maryland School of Medicine, and Dr. Yu Chen, University of Maryland College Park)
The vessel shown in the videos below was located in a deep sulcus in the parietal lobe of a sheep.
- Doppler OCT greatly enhances the detectability of small arteries in the brain: The video to the left shows the standard OCT sequence as the OCT probe approach a small artery ~200 microns in diameter. The video to the right shows the Doppler signal. The strong pulsations clearly shows it is an artery rather than a vein. The information for both videos is gathered at the same time by the needle probe, but displayed separately here. There is still a ‘bug’ in the display that limits the intuitive nature of the display. Because the flow is high, the Doppler signal “wraps around” (rainbow effect). We are currently developing an algorithm to “unwrap” the Doppler signal. Nevertheless, the current imperfect Doppler display is still able to demonstrate the ability to visualize small arteries.
- The needle type OCT probe can push the artery aside without lacerating the vessel: This is the continuation of the previous video. After judging that the center of the artery is off to the side of the probe trajectory, we predicted that the probe would simply push the vessel aside. We demonstrate this in this video. We then pulled back the probe and the vessel could be seen again intact (not shown here). This is the first demonstration of what neurosurgeons long suspected, stereotactic probes must push vast majority of arteries to the side in order to explain the relatively low rate of hemorrhages in the face of high densities of vessels in the brain. One question we seek to answer is “What are the conditions where vessels will lacerate?”
The combination of forward-scanning OCT and OCT Doppler imaging allows us to differentiate veins from arteries in front of the advancing probe. [See videos differentiating veins and arteries using forward scanning OCT.]
Mapping Basal Ganglia Structures and Differentiating Tracts
(Work-in-progress in collaboration with Dr. Cha-Min Tang, University of Maryland School of Medicine)
Originally, we cut 100 um sections of human basal ganglia to construct a high resolution 3D atlas of the human basal ganglia. We found that when light struck the sections from different angles, the images showed distinct white mater tracts within the internal capsule based. We concluded that we could use this information to deduce the trajectory of the fiber through the section and thus reconstruct distinct fiber tracts within the internal capsule – tracts that previously had not been resolved by standard techniques. This property called optical anisotropy can be seen in this video where the light is being projected onto the slide from different angles.
By reconstructing these fibers through sequential sections, we can elucidate a number of tracts shown in the images and videos below.
The pedunculopontine nucleus (PPN) has garnered considerable interest, because it's the only target by which deep brain stimulation (DBS) can substantially ameliorate the gait disturbances of Parkinson's disease. But no one has been able to visualize its connections in the human brain. With unprecedented resolution and precision, our method elucidates the distinct projections of the PPN. As can be seen in the image below and this video.
- The green and red surfaced-rendered structures are the subthalamic (STN) and red nuclei, respectively.
- The orange volume-rendered cloud represents dopaminergic cells of the substantianigra (SN).
- The blue volume-rendered cloud represents choline-acetyltransferase-positive cells of the PPN.
- Tracts with poorly saturated colors represented poorly myelinated projections.
- The pale blue tracts represent the pedunculosubthalamic fibers, connecting the PPN and the STN.
- The pale yellow tracts represent the pedunculothalamic fibers, connecting the PPN and thalamus.
- The pale orange tracts represent the connections between the PPN and the SN. The pale green tracts represent the connections between the STN and the SN.
- The gray and black surfaced rendered structures are the anterior and posterior commissures, respectively, rendered for the purpose of anatomical orientation.
Other tract segments are arbitrarily highlighted with colors of full saturation, to indicate myelination. The internal capsule is purple, the subthalamic fasciculus red, the lenticular fasciculus cyan, and thalamic tracts orange.
L-mode of pass through NHP brain with corresponding B-mode images shows how distinct different regions look on OCT:
Liang C-P, Wierwille J, Moreira T, Schwartzbauer G, Jafri MS, Tang C-M, Chen Y. A forward-imaging needle-type OCT probe for image guided stereotactic procedures. Optics Express, 19(27), 26283-94, 2011.
McDowell KA, Shen W-B, Siebert AS, Clark SM, Dugger NV, Valentino KM, Wilson JM, Jinnah HA, Fishman PS, Shaw CA, Jafri MS, Yarowsky PJ, Environmental neurotoxin-induced progressive model of parkinsonism in rats, Annals of Neurology, 68, 70-80, 2010.
- Published responses to letters to the editor for the above paper:
- McDowell KA, Shen W-B, Siebert AS, Clark SM, Jinnah HA, Sztalryd C, Fishman PS, Shaw CA, Jafri MS, Yarowsky PJ, Washed cycad flour contains b-N-methylamino-LAlanine and may explain Parkinsonian symptoms, Annals of Neurology, 69(2), 423-4, 2011.
- McDowell KA, Shen W-B, Siebert AS, Clark SM, Jinnah HA, Sztalryd C, Fishman PS, Shaw CA, Jafri MS, Yarowsky PJ, Neurotoxic cycad components and Western Pacific ALS/PDC, Annals of Neurology, 68(6), 976, 2010.
Siebert AS, Desai V, Chandrasekaran K, Fiskum G, Jafri MS, Nrf2 activators provide neuroprotection against 6-hydroxydopamine toxicity in rat organotypic nigrostriatal co-cultures, Journal of Neuroscience Research, 87(7), 1659-69, 2009.
Jafri MS, Tang R, Tang C-M, Optical coherence tomography guided neurosurgical procedures in small rodents, Journal of Neuroscience Methods, 176(2), 85-95, 2009.
Lin J, Staecker H, Jafri MS. OCT imaging of the inner ear: A feasibility study with implications for cochlear implantation, Annals of Otology, Rhinology & Laryngology, 117, 341-6, 2008.
Laing JM, Golembewski EK, Wales SQ, Liu J, Jafri MS, Yarowsky PJ, Aurelian L. The growth compromised HSV-2 vector Î”RR protects from NMDA-induced neuronal degeneration through redundant activation of the MEK/ERK and PI3-K/Akt survival pathways either one of which overrides apoptotic cascades, Journal of Neuroscience Research, 86(2), 378-91, 2008.
Burris N, Schwartz K, Tang C-M., Jafri MS, Schmitt J, Kwon MH, Toshinaga O, Gu J, Brown J, Brown E, Pierson R, Poston R. Catheter-Based Infrared Light Scanner as a Tool to Assess Conduit Quality in Coronary Artery Bypass Surgery, Journal of Thoracic and Cardiovascular Surgery, 133(2), 419-27, 2007.
Jafri MS, Schmitt JM, Farhang S, Tang RS, Desai N, Fishman PS, Rohwer RG, Tang C-M, Optical coherence tomography in the diagnosis and treatment of neurological disorders, Journal of Biomedical Optics, 10(5), 051603(1-11), 2005.
Caicedo A, Jafri MS, Roper SD, In situ imaging reveals neurotransmitter receptors for glutamate in taste receptor cells, Journal of Neuroscience, 20(21), 7978-7985, 2000.
Jafri MS and Weinreich D, Substance P regulates IK and Ih decreases excitability of ferret vagal sensory neurons via a NK-1 receptor, Journal of Neurophysiology, 79, 769-777, 1998.
Jafri MS, Moore KA, Taylor GE, Weinreich D, Histamine H1 receptor activation blocks two classes of potassium current, IK(leak) and IAHP, to excite ferret vagal afferents, Journal of Physiology (London), 503(3), 533-546, 1997.
Cohen AS, Moore KA, Bangalore R, Jafri MS, Weinreich D, Kao JPY, Ca2+-induced Ca2+ release mediates Ca2+ transients evoked by single action potentials in rabbit vagal afferent neurones, Journal of Physiology (London), 499(2), 315-28, 1997.
Jafri MS and Weinreich D, Substance P hyperpolarizes vagal sensory neurones of the ferret, Journal of Physiology (London), 493(1), 157-66, 1996. [Published erratum, Journal of Physiology (London), 494(3)]
Isenberg KE, Ukhun IA, Holstad SG, Jafri S, Uchida I, Zorumski CF, Yang J, Partial cDNA cloning and NGF regulation of a rat 5-HT3 receptor subunit, Neuroreport, 5(2), 121-4, Nov 1993.
Wiggins RE, Jafri MS, Proia AD, 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid is a more potent neutrophil chemoattractant than the 12(R) epimer in the rat cornea, Prostaglandins, 40(2), 131-41, Aug 1990.
Hall IH, Spielvogel BF, Sood A, Ahmed F, Jafri S, Hypolipidemic activity of trimethylamine-carbomethoxyborane and related derivatives in rodents, J Pharm Sc, 76(5), 359-65, 1987.
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