Mithilesh K Das

Purdue University, West Lafayette, IN, United States

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Publications (53)166.78 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Bi-ventricular (BiV) pacing is an effective therapy for the treatment of cardiac electromechanical (EM) dysfunction. The reason(s), however, for therapy non-response in approximately one-third of the subjects remains unclear, especially as it relates to myocardial perfusion and pacing location. In this study, we examined how acute BiV pacing response may be related to underlying myocardial perfusion coupled with pacing near or distant to the area of perfusion. In 10 open-chest anesthetized canines, coronary blood flow to the left ventricular (LV) anterior wall (AW: n = 5) and lateral wall (LW: n = 5) was controlled during four pacing conditions: right atrial, right ventricular (pseudo-left bundle branch block; [pseudo-LBBB]), BiV-LW and BiV-AW. Local EM function (piezo-electrical crystals and electrodes), along with global hemodynamic parameters, were measured during all pacing conditions at three coronary perfusion rates (≥0.40 mL/min/g, 0.20-0.40 mL/min/g and <0.20 mL/min/g). A positive BiV therapy response was assessed by a significant increase in the maximum cardiac output compared with the pseudo-LBBB condition. Despite no improvement in QRS duration, BiV-LW pacing improved LV function compared with the pseudo-LBBB pacing condition (P value <0.01). This improvement with BiV-LW pacing was seen above a certain myocardial perfusion threshold and was independent of any increases in regional coronary blood flow with BiV pacing. At lower myocardial perfusion rates, LV function was not improved with BiV pacing at any location. This study underscores the significance of even mild ischemia on BiV pacing response.
    Experimental Biology and Medicine 06/2012; 237(6):644-51. · 2.80 Impact Factor
  • Mithilesh Kumar Das
    Heart rhythm: the official journal of the Heart Rhythm Society 01/2012; 9(6):936-7. · 4.56 Impact Factor
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    ABSTRACT: The risk of myocardial penetration due to active-fixation screw-in type pacing leads has been reported to increase as the helix electrodes become smaller. In order to understand the contributing factors for lead penetration, we conducted finite element analyses of acute myocardial micro-damage induced by a pacemaker lead screw-in helix electrode. We compared the propensity for myocardial micro-damage of seven lead designs including a baseline model, three modified designs with various helix wire cross-sectional diameters, and three modified designs with different helix diameters. The comparisons show that electrodes with a smaller helix wire diameter cause more severe micro-damage to the myocardium in the early stage. The damage severity, represented by the volume of failed elements, is roughly the same in the middle stage, whereas in the later stage the larger helix wire diameter generally causes more severe damage. The onset of myocardial damage is not significantly affected by the helix diameter. As the helix diameter increases, however, the extent of myocardial damage increases accordingly. The present findings identified several of the major risk factors for myocardial damage whose consideration for lead use and design might improve acute and chronic lead performance.
    Journal of Biomechanical Engineering 06/2011; 133(6):061006. · 1.52 Impact Factor
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    ABSTRACT: Although left ventricular (LV) coronary sinus lead dislodgement remains a problem, the risk factors for dislodgement have not been clearly defined. In order to identify potential risk factors for acute lead dislodgement, we conducted dynamic finite element simulations of pacemaker lead dislodgement in marginal LV vein. We considered factors such as mismatch in lead and vein diameters, velocity of myocardial motion, branch angle between the insertion vein and the coronary sinus, degree of slack, and depth of insertion. The results show that large lead-to-vein diameter mismatch, rapid myocardial motion, and superficial insertion are potential risk factors for lead dislodgement. In addition, the degree of slack presents either a positive or negative effect on dislodgement risk depending on the branch angle. The prevention of acute lead dislodgment can be enforced by inducing as much static friction force as possible at the lead-vein interface, while reducing the external force. If the latter exceeds the former, dislodgement will occur. The present findings underscore the major risk factors for lead dislodgment, which may improve implantation criterion and future lead design.
    Journal of Biomechanical Engineering 03/2011; 133(3):031006. · 1.52 Impact Factor
  • Saurabh Malhotra, Mithilesh K Das
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    ABSTRACT: In the USA, two-thirds of sudden cardiac deaths (SCDs) are caused by sustained ventricular tachycardia and ventricular fibrillation. Implantable cardioverter defibrillator (ICD) therapy has been demonstrated to decrease mortality caused by these arrhythmias, when used both for primary and secondary prevention. However, ICD use is expensive, has proarrhythmic effects and does not prevent ventricular arrhythmias. Antiarrhythmic drugs (AADs) can be used for acute or chronic therapy to prevent ventricular arrhythmias and SCD. Most commonly, AADs are often used in patients with an ICD who have recurrent ICD shocks due to ventricular arrhythmias. Class I AADs are used in patients with a structurally normal heart and are contraindicated in patients with structural heart disease. β-blockers have been demonstrated to be beneficial in preventing mortality and malignant tachyarrhythmias in postmyocardial infarction and congestive heart failure patients, and in patients who have an ICD. Amiodarone has a neutral effect on mortality, while other class III drugs may increase mortality in certain subgroups of patients. Dronedarone, a new class III drug, may reduce mortality, but sufficient data are not available to allow for its use in the prevention of malignant tachyarrhythmias. Few drugs that are not classified as AADs can also prevent arrhythmias, via their beneficial effects on cardiovascular remodeling. These non-ADDs have delayed and indirect effects, which are mediated by the renin-angiotensin-aldosterone system and lipid metabolism - n-3 polyunsaturated fatty acids (fish oil), and statins, and can thus can reduce the likelihood of future malignant ventricular arrhythmias in patients with coronary artery disease or congestive heart failure. The role of chronic drug therapy alone for primary and secondary prevention of SCD is less than desirable because of proarrhythmic and adverse side effects. The non-ADDs are well tolerated and have no proarrhythmic actions, thus their benefit could outweigh risks, although currently there are no concrete data to suggest this.
    Future Cardiology 03/2011; 7(2):203-17.
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    ABSTRACT: T-wave alternans (TWA) increases before ventricular tachycardia (VT) or fibrillation (VF), suggesting that it may warn of VT/VF in implantable cardioverter-defibrillator patients. Recently, we described a method for measuring alternans and nonalternans variability (TWA/V) from electrograms (EGMs) stored in implantable cardioverter-defibrillators before VT/VF. The goal of this prospective, multicenter study was to determine whether EGM TWA/V was greater before VT/VF than at baseline. We enrolled 63 implantable cardioverter-defibrillator patients. TWA/V was computed from stored EGMs before spontaneous VT/VF and from sequential windows of 8 pairs of beats using 4 different control recordings: baseline rhythm, rapid pacing at 105 bpm, segments of ambulatory Holter EGMs matched to the time of VT/VF episodes, and EGMs before spontaneous supraventricular tachycardia. During follow-up, 28 patients had 166 episodes of VT/VF. TWA/V was greater before VT/VF (62.9 ± 3.1 μV; n = 28) than during baseline rhythm (12.8 ± 1.8 μV; P < 0.0001; n = 62), during rapid pacing (14.5 ± 2.0 μV; P < 0.0001; n = 52), before supraventricular tachycardia (27.5 ± 6.1 μV; P < 0.0001; n = 9), or during time-matched ambulatory controls (12.3 ± 3.5 μV; P < 0.0001; n = 16). By logistic regression, the odds of VT/VF increased by a factor of 2.2 for each 10-μV increment in TWA/V (P < 0.0001). In implantable cardioverter-defibrillator patients, EGM TWA/V is greater before spontaneous VT/VF than in control recordings. Future implantable cardioverter-defibrillators that measure EGM TWA/V continuously may warn patients and initiate pacing therapies to prevent VT/VF.
    Circulation 02/2011; 123(10):1052-60. · 15.20 Impact Factor
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2011; 57(14).
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    ABSTRACT: Nonischemic dilated cardiomyopathy (NICM) is associated with diffuse global hypokinesia on echocardiography. However, NICM also may be associated with segmental wall-motion abnormalities (SWMAs) even in the presence of global hypokinesia, probably secondary to patchy myocardial scars. Because myocardial scars serve as substrate for reentry, the purpose of this study was to determine whether SWMA is a predictor of ventricular arrhythmic events in NICM. Echocardiographic parameters and appropriate implantable cardioverter-defibrillator (ICD) therapy for arrhythmic events (shock or antitachycardia pacing) were studied in NICM patients with an ICD. Two-dimensional echocardiography of the left ventricle was recorded in a 16-segment model. SWMA was defined by the presence of akinesia or moderate to severe hypokinesia in at least two segments. Patients were divided into one of two groups according to the presence (SWMA group) or the absence (non-SMWA group) of SWMA. SWMA was present in 47.5% of 101 patients (mean age 58.0 ± 15.6 years, 85% male, primary prophylaxis indication 46%, mean ejection fraction 26% ± 9%, mean follow-up 29 ± 18.4 months) studied. No significant difference in mean age, ejection fraction, and QRS duration was seen between SWMA and non-SWMA groups. The SWMA group had a significantly higher incidence of arrhythmic events than did the non-SWMA group (65% vs 15%, P <.001). Kaplan-Meier survival analysis revealed that SMWA was associated with significantly reduced time to first arrhythmic event (P = .001). SWMA (P <0.001), New York Heart Association heart failure class (P = .016), and secondary prevention indication for ICD placement (P = .005) were significant independent predictors of an arrhythmic event. SWMA did not predict mortality. SWMA is an independent predictor of arrhythmic events in patients with NICM.
    Heart rhythm: the official journal of the Heart Rhythm Society 10/2010; 7(10):1390-5. · 4.56 Impact Factor
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    ABSTRACT: Various diagnostic maneuvers have been proposed to help differentiate orthodromic reciprocating tachycardia (ORT) from atrioventricular nodal reentrant tachycardia (AVNRT) prior to ablation. However, not all criteria are applicable in every situation as each has limitations. The purpose of this study was to determine whether the behavior of tachycardia during onset of right ventricular (RV) pacing would help differentiate ORT from AVNRT. We retrospectively reviewed 72 cases (42 typical AVNRT, 7 atypical AVNRT, 15 left free-wall pathways, 6 septal pathways, 2 right free-wall pathways). We assessed the number of beats required to accelerate the tachycardia cycle length (TCL) to the paced cycle length (PCL) once a fully RV paced complex was achieved during supraventricular tachycardia. In the AVNRT group, delta cycle length (DCL = PCL-TCL) was 29 +/- 16 ms compared to 29 +/- 10 ms in ORT group (P = NS). In the AVNRT group, the average number of fully RV paced beats required to reset the tachycardia was 3.7 +/- 1.1 compared to 1 +/- 0 in the ORT group (P <.0001). Using a cutoff >1 beat yielded both positive and negative predictive values of 100% for diagnosing AVNRT versus ORT. During entrainment attempts, AVNRT terminated 51% of the time and ORT terminated 65% of the time but still allowed application of the new criterion. Assessing timing and type of response of supraventricular tachycardia to RV pacing can help differentiate ORT from AVNRT with high certainty and prevent the need for other pacing maneuvers and measurements.
    Heart rhythm: the official journal of the Heart Rhythm Society 09/2010; 7(9):1326-9. · 4.56 Impact Factor
  • Mithilesh K Das, Douglas P Zipes
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    ABSTRACT: Life-threatening ventricular arrhythmias such as sustained ventricular tachycardia and ventricular fibrillation are responsible for two thirds of sudden cardiac deaths annually in the United States. Implantable cardioverter-defibrillator (ICD) therapy prevents mortality from arrhythmic death but is expensive and has some associated morbidity from proarrhythmia and mechanical malfunction. Furthermore, ICDs treat ventricular arrhythmias but do not prevent them. Antiarrhythmic drugs (AADs) can be used for acute or chronic therapy to prevent ventricular arrhythmias and sudden cardiac deaths. AADS are often used in patients with an ICD who have recurrent ICD shocks resulting from ventricular arrhythmias. Class I AADs are contraindicated in patients with structural heart disease. Other than amiodarone, all Class III drugs have either a neutral or deleterious effect on mortality. Dronedarone, a new Class III drug, may reduce mortality, but more information is needed to be sure. A class of drugs that do not qualify as an AAD can modify cardiovascular remodeling processes and have a delayed and indirect antiarrhythmic effect. These so-called "nonantiarrhythmic drugs" such as drugs acting on the renin-angiotensin-aldosterone system, fish oil, and statins can reduce the likelihood of future ventricular tachycardia/ventricular fibrillation in patients with coronary artery disease or congestive heart failure. The role of AADs for chronic therapy for primary and secondary prevention of sudden cardiac death is problematic because of proarrhythmia and adverse side effects. Because these nonantiarrhythmic drugs are well tolerated and have no proarrhythmic actions, their benefits should outweigh risks.
    Journal of cardiovascular pharmacology 05/2010; 55(5):438-49. · 2.83 Impact Factor
  • Mithilesh K Das, Luis R Scott, John M Miller
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    ABSTRACT: Re-entry is the most common mechanism of sustained monomorphic ventricular tachycardia (VT) in patients with coronary artery disease and prior myocardial infarction (MI). This study sought to report the electrophysiological properties of a series of patients with prior MI who underwent radiofrequency ablation (RFA) for VT originating instead from a focal source. The electrophysiological properties of 46 patients with prior MI (male 89%, age 64.8 +/- 10.2 years) who underwent RFA for sustained VT were studied. A total of 101 VTs were induced (92 [91%] macro-re-entrant VT and 9 [9%] focal VT). One patient had adenosine-sensitive idiopathic focal VT. The focal VT group had a significantly shorter pre-systolic interval (electrogram to QRS) during VT compared with the macro-re-entrant VT group (36 +/- 17 ms vs. 117 +/- 67 ms, P = .001). The successful ablation sites in the focal VT group also had a significantly lower ratio (in percentage) of electrogram-QRS interval to diastolic interval (VT cycle length - QRS duration) during VT (14 +/- 8%) as compared with macro-re-entrant VTs (48 +/- 30%, P <.001). Focal VTs demonstrated an apparent point source of endocardial activation and could not be entrained, whereas 77% of macro-re-entrant VTs were entrained. Successful ablation sites for focal VT (success rate 100%) were predominantly in the basal half of the left ventricle (75%), whereas only 60% of macro-re-entrant VTs (success rate 90.7%) were basal (P = .01). However, the procedure time, VT cycle length, number of RFA applications required for success, and acute success results were not significantly different in these 2 groups. A focal mechanism is present in up to 9% of VTs in patients with CAD and prior MI that are induced during electrophysiology study for RF ablation. Mechanistic distinction from more typical macro-re-entrant VT in this population is important because ablation site characteristics are very different.
    Heart rhythm: the official journal of the Heart Rhythm Society 03/2010; 7(3):305-11. · 4.56 Impact Factor
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    ABSTRACT: Myocardial scar is a substrate for reentrant ventricular arrhythmias and is associated with poor prognosis. Fragmented QRS (fQRS) on 12-lead ECG represents myocardial conduction delays due to myocardial scar in patients with coronary artery disease (CAD). The purpose of this study was to determine whether fQRS is associated with increased ventricular arrhythmic event and mortality in patients with CAD and nonischemic dilated cardiomyopathy (DCM). Arrhythmic events and mortality were studied in 361 patients (91% male, age 63.3 +/- 11.4 years, mean follow-up 16.6 +/- 10.2 months) with CAD and DCM who received an implantable cardioverter-defibrillator for primary or secondary prophylaxis. fQRS included various RSR' patterns (QRS duration <120 ms), such as > or =1 R prime or notching of the R wave or S wave present on at least two contiguous leads of those representing anterior (V(1)-V(5)), lateral (I, aVL, V(6)), or inferior (II, III, aVF) myocardial segments. fQRS was present in 84 (23%) patients (fQRS group) and absent in 100 (28%) patients (non-fQRS group). Wide QRS (wQRS; QRS duration > or =120 ms) was present in 177 (49%) patients. Kaplan-Meier analysis revealed that event-free survival for an arrhythmic event (implantable cardioverter-defibrillator shock or antitachycardia pacing) was significantly lower in the fQRS group than in the non-fQRS and wQRS groups (P <.001 and P <.019, respectively). fQRS was an independent predictor of an arrhythmic event but not of death. fQRS on 12-lead ECG is a predictor of arrhythmic events in patients with CAD and DCM. fQRS is associated with a significantly decreased time to first arrhythmic event compared with non-fQRS and wQRS.
    Heart rhythm: the official journal of the Heart Rhythm Society 01/2010; 7(1):74-80. · 4.56 Impact Factor
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2010; 55(10).
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    Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2010; 55(10).
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    Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2010; 55(10).
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    ABSTRACT: During a normal lifetime, the heart may beat over 2 billion times, but the mechanisms by which the heart beats are initiated remain a subject of intense investigation. Since the discovery of a pacemaker current (I(f)) in 1978, multiple studies have shown that rhythmic changes in membrane voltage (the "membrane voltage clock") underlie the mechanisms of automaticity. The I(f) is a depolarization current activated during hyperpolarization. Therefore, when the cardiac cells recover, the I(f) is activated and slowly depolarizes the cell membrane, leading to the onset of action potential. Recent studies, however, suggest that increased intracellular Ca (Ca(i)) induced by spontaneous rhythmic sarcoplasmic reticulum Ca release (the "calcium clock") is also jointly responsible for the initiation of the heart beat. Elevated Ca(i) activates another ionic current (the sodium-calcium exchanger current or I(NCX)), leading to spontaneous phase 4 depolarization. Under normal conditions, both clocks are needed to initiate the heart beat. Malfunction of the clocks is associated with sinus node dysfunction in heart failure and atrial fibrillation. More studies are needed to determine how both clocks work together to initiate heart beat under normal and disease conditions.
    Circulation Journal 12/2009; 74(2):221-5. · 3.58 Impact Factor
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    ABSTRACT: Electrocardiographic signs of a non-ST elevation myocardial infarction (NSTEMI) are nonspecific, and therefore the diagnosis of NSTEMI during acute coronary syndromes (ACS) depends mainly on cardiac biomarker levels. Fragmented QRS (fQRS) represents myocardial conduction abnormalities due to myocardial infarction (MI) scars in patients with coronary artery disease. However, the time of appearance of fQRS during ACS has not been investigated. It was postulated that in patients with ACS, fQRS on 12-lead electrocardiography occurs within 48 hours of presentation with NSTEMI as well as ST elevation MI and that fQRS predicts mortality. Serial electrocardiograms from 896 patients with ACS (mean age 62 +/- 11 years, 98% men) who underwent cardiac catheterization were studied. Four hundred forty-one patients had MIs, including 337 patients with NSTEMIs, and 455 patients had unstable angina (the control group). Serial electrocardiograms were obtained every 6 to 8 hours during the first 24 hours after the diagnosis of MI and the next day (<48 hours). Fragmented QRS on 12-lead electrocardiography was defined by the presence of single or multiple notches in the R or S wave, without a typical bundle branch block, in > or =2 contiguous leads in 1 of the major coronary artery territories. Fragmented QRS developed in 224 patients (51%) in the MI group and only 17 (3.7%) in the control group (p <0.001). New Q waves developed in 122 (28%), 76 (23%), and 2 (0.4%) patients in the MI, NSTEMI, and control groups, respectively. The sensitivity values of fQRS for ST elevation MI and NSTEMI were 55% and 50%, respectively. The specificity of fQRS was 96%. Kaplan-Meier survival analysis revealed that patients with fQRS had significantly decreased times to death compared to those without fQRS. Fragmented QRS, T-wave inversion, and ST depression were independent predictors of mortality during a mean follow-up period of 34 +/- 16 months. In conclusion, fQRS on 12-lead electrocardiography is a moderately sensitive but highly specific sign for ST elevation MI and NSTEMI. Fragmented QRS is an independent predictor of mortality in patients with ACS.
    The American journal of cardiology 12/2009; 104(12):1631-7. · 3.58 Impact Factor
  • Mithilesh Kumar Das
    Cardiology 10/2009; 115(1):37-8. · 1.52 Impact Factor
  • Mithilesh K DAS, Gopi Dandamudi, Hillel A Steiner
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    ABSTRACT: In recent years, the role of implantable pacing devices has expanded beyond the arrhythmia horizon and contemporary pacemakers' attempt to meet the physiological needs of patients. Modern pacemakers' functions include various modes of dual-chamber pacing, rate-response algorithms with dual sensors for optimum physiological response, cardiac resynchronization therapy (CRT), arrhythmia-prevention algorithms, antitachycardia pacing, and hemodynamic monitoring. The automaticity features of pacemakers enable continuous or intermittent monitoring of various pacemaker parameters including battery voltage, pacing impedance, sensing levels, pacing thresholds, and daily activity log. Modern pacemakers offer "physiological pacing" algorithms that minimize ventricular pacing and reduce the incidence of atrial fibrillation significantly. Ventricular pacing in patients with intact atrioventricular (AV) conduction or intermittent advanced AV block should be minimized with a hope to reduce heart failure hospitalization and mortality. A reduction in all-cause mortality due to physiological pacing, except for the CRT, has yet to be demonstrated in a randomized trial. Overall, modern pacemakers have acceptable performances to fulfill the clinical needs and have a reasonable safety margin. Promising new technologies are currently under development and offer hope to patients who may one day derive both symptomatic and mortality benefit from these devices.
    Pacing and Clinical Electrophysiology 10/2009; 32(9):1207-21. · 1.75 Impact Factor
  • Mithilesh K Das, Hicham El Masry
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    ABSTRACT: Several invasive and noninvasive tests for risk stratification of sudden cardiac death (SCD) have been studied. Tests such as microwave T wave alternans (repolarization abnormality) and signal-averaged ECG (depolarization abnormality) have high negative predictive values but low positive predictive values in patients with heart disease. The presence of a fragmented QRS (fQRS) complex on a routine 12-lead ECG is another marker of depolarization abnormality. The purpose of this review is to discuss the potential utility of tests to detect depolarization abnormalities of the heart for the risk stratification of mortality and SCD with main emphasis on fQRS. fQRS is associated with increased mortality and arrhythmic events in patients with coronary artery disease. fQRS has also been defined as a marker of arrhythmogenic right ventricular cardiomyopathy and Brugada syndrome. In Brugada syndrome, the presence of fQRS predicts episodes of ventricular fibrillation during follow-up. fQRS may be of value in determining the risk for SCD and guiding selection for device therapy in patients with structural heart disease and Brugada syndrome. It is possible that the predictive value of fQRS for SCD can be enhanced further by combining a marker of repolarization abnormality such as microwave T wave alternans.
    Current opinion in cardiology 10/2009; 25(1):59-64. · 2.66 Impact Factor

Publication Stats

568 Citations
166.78 Total Impact Points

Institutions

  • 2012
    • Purdue University
      • Weldon School of Biomedical Engineering
      West Lafayette, IN, United States
  • 2010–2012
    • Richard L. Roudebush VA Medical Center
      Indianapolis, Indiana, United States
  • 2007–2011
    • Indiana University-Purdue University School of Medicine
      • Department of Medicine
      Indianapolis, Indiana, United States
  • 2004–2011
    • Indiana University-Purdue University Indianapolis
      • • Department of Biomedical Engineering
      • • Department of Medicine
      Indianapolis, IN, United States
  • 2009
    • Wayne State University
      Detroit, Michigan, United States
    • University of Leipzig
      Leipzig, Saxony, Germany