People

Faculty

Rahim R. Rizi
Professor
Email Rahim R. Rizi
215-615-2426

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Rahim R. Rizi
Professor
rizi@uphs.upenn.edu
215-615-2426

The primary mission of the Functional and Metabolic Imaging Group (FMIG) is the development and application of novel hyperpolarized MRI techniques to the diagnosis of various pulmonary and metabolic disorders. Hyperpolarization, the process of drastically increasing the population difference between nuclear spin states, provides a platform for imaging lung physiology and metabolic activity with spatial and temporal resolution unattainable with conventional MRI techniques, thus offering the potential for the earlier diagnosis of disease states and the precise monitoring of a patient's response to medical treatment. This core research theme is executed with an eye toward several ultimate goals: the identification of changes in pulmonary structure and function associated with disease, a more complete understanding of pathogenesis, and the establishment of a more sensitive testing environment to develop treatments for lung disease. To date, significant contributions in these areas include new imagining techniques for the comprehensive description of lung physiology and structure, accurate imaging of the regional pulmonary partial pressure of oxygen in both humans and large and small animals, highly developed imaging of regional ventilation, and a state-of-the-art mechanical ventilation device. Specifically, our research activities at FMIG is divided into four general branches:
1. The development of novel imaging techniques for the quantitative assessment of pulmonary structure and function: Important pulmonary physiology parameters, such as ventilation, blood/air gas exchange, inflammation, and perfusion, can be monitored and quantified with high spatial and temporal resolution through the use of hyperpolarized gas (3He and 129Xe) MRI. (Perfusion may also be imaged with hyperpolarized 13C MRI.) These methods of measurement are employed in the study of common pulmonary disease models: most notably, COPD, emphysema, asthma, and cystic fibrosis. In parallel, FMIG is investigating the use of hyperpolarized 13C-bicarbonate for imaging regional pulmonary pH, an important indicator for a number of pathologies.
2. The development of novel methods for real-time metabolic imaging: Hyperpolarized13C MRI has strong potential for the real-time imaging of metabolic activity in vitro and in vivo. Hyperpolarized 13C-labeled metabolites (e.g., [1-13C]pyruvate) can be delivered to a living subject or a cell culture and subsequently used to detect aberrant metabolism, which is a key pathological indication for a number of disease states, including cancer. This research objective includes the in vitro characterization of 13C imaging agents under physiological conditions and the more extreme conditions typical to hyperpolarization techniques.
3. The construction of novel polarization apparatuses: FMIG intends to build a novel13C DNP research polarizer that improves upon commercial polarization apparatuses in two ways. Firstly, the new polarizer will be capable of the high-throughput needed to dramatically improve in vivo studies. Secondly, the polarizer will provide control of hyperpolarization parameters (most importantly, field strength), allowing the researchers to probe the limiting factors of polarization and develop new 13C tracers and measurement techniques for studying the respiratory system.
4. The development and implementation of rapid imaging pulse sequences: Because of the loss of signal (longitudinal relaxation) with time inherent to hyperpolarized MRI, FMIG builds pulse sequences specially suited to rapid imaging.
Stephen Kadlecek
Associate Professor
Email Stephen Kadlecek
215-746-4677

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Stephen Kadlecek
Associate Professor
stephen.kadlecek@uphs.upenn.edu
215-746-4677

My primary research focus is the development of techniques to image lung function, metabolism, energy status and inflammatory activity. Based on my formal training in atomic and molecular physics, I initially worked to understand and optimize methods for aligning nuclei of biologically relevant atoms using light (see publications 1,2, below), parahydrogen (3,4) or microwaves and cryogenic temperatures (5,6). This motivated a series of isolated organ (7,8), preclinical (9,10) and clinical (11,12) studies in which we tested these ‘hyperpolarized’ agents for sensitivity to disease in comparison to current clinical tests, and for the potential to physiologically perturb the system under study. Having shown the clinical applicability of these imaging methods, my current goals are to:

1) extend the range of functional and metabolic MRI to other disease states, physiological conditions and organ systems via continued preclinical experiments.

2) enable clinical imaging in pediatric and compromised populations using robust sequences and agent delivery methods.

3) refine metabolic imaging techniques and the available contrast agents such that recent physics advances can be brought to the clinic in a safe and cost-effective way.

Selected publications:

1. Kadlecek S, Anderson LW, Erickson CJ, Walker TG: Spin Relaxation in Alkali-Metal 1-Sigma+g Dimers. Phys Rev A 64(5): 052717, Oct 2001.

2. Kadlecek S, Walker T, Walter DK, Erickson C, Happer W: Spin-axis Relaxation in Spin-Exchange Collisions of Alkali-Metal Atoms. Phys Rev A 63(6): 052717, Apr 2001.

3. Kadlecek S, Vahdat V, Nakayama T, Ng D, Emami K, Rizi R: A simple and low-cost device for generating hyperpolarized contrast agents using parahydrogen. NMR Biomed 24(8): 933-42, Oct 2011

4. Kadlecek S, Emami K, Ishii M, Rizi R: Optimal transfer of spin-order between a singlet nuclear pair and a heteronucleus. J Magn Reson 205(1): 9-13, Mar 2010

5. Kuzma NN, Håkansson P, Pourfathi M, Ghosh RK, Kara H, Kadlecek SJ, Pileio G, Levitt MH, Rizi RR: Lineshape-based polarimetry of dynamically-polarized ¹⁵N₂O in solid-state mixtures. J Magn Reson 234: 90-94, Nov 2013

6. Pourfathi M, Kuzma NN, Kara H, Ghosh RK, Shaghaghi H, Kadlecek SJ, Rizi RR: Propagation of dynamic nuclear polarization across the xenon cluster boundaries: elucidation of the spin-diffusion bottleneck. J Magn Reson 235: 71-76, Oct 2013

7. Kadlecek S, Shaghaghi H, Siddiqui S, Profka H, Pourfathi M, Rizi R: The effect of exogenous substrate concentrations on true and apparent metabolism of hyperpolarized pyruvate in the isolated perfused lung. NMR Biomed 27(12): 1253- 1270, Dec 2014

8. Shaghaghi H, Kadlecek S, Siddiqui S, Pourfathi M, Hamedani H, Clapp J, Profka H, Rizi R: Ascorbic acid prolongs the viability and stability of isolated perfused lungs: A mechanistic study using ³¹P and hyperpolarized ¹³C nuclear magnetic

resonance. Free Radic Biol Med 10(89): 62-71, Dec 2015

9. Kadlecek S, Mongkolwisetwara P, Xin Y, Ishii M, Profka H, Emami K, Rizi R: Regional determination of oxygen uptake in rodent lungs using hyperpolarized gas and an analytical treatment of intrapulmonary gas redistribution. NMR Biomed

24(10): 1253-63, Dec 20119. Hamedani H, Kadlecek S, Ruppert K, Xin Y, Duncan I, Rizi R:

10. Ventilation Heterogeneity Imaged by Multibreath Wash-ins of Hyperpolarized ³He and ¹²⁹Xe in Healthy Rabbits. J Physiol in press, Jul 2021.

11. Baron RJ, Hamedani H, Kadlecek SJ, Duncan IF, Xin Y, Siddiqui S, Pourfathi M, Cereda M, Rizi RR: A Model for Predicting Future FEV1 Decline in Smokers Using Hyperpolarized 3He Magnetic Resonance Imaging. Acad Radiol 26(3): 383-394, Mar 2019

12. Hamedani H, Kadlecek SJ, Ishii M, Xin Y, Emami K, Han B, Shaghaghi H, Gopstein D, Cereda M, Gefter WB, Rossman MD, Rizi RR: Alterations of regional alveolar oxygen tension in asymptomatic current smokers: assessment with hyperpolarized ³He MR imaging. Radiology 274(2): 585-596, Feb 2015
Kai Ruppert
Assistant Professor
Email Kai Ruppert

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Kai Ruppert
Assistant Professor
Kai.Ruppert@uphs.upenn.edu

Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) provide fascinating tools for looking at the inside of the human body and assessing what changes occur through normal aging or in disease without using potentially harmful ionizing radiation. Conventional MRI uses the protons from water and fat molecules in the body as signal sources. For this reason, it is challenging to image the airspaces in our body, in particular the lung.

The focus of my research is to obtain information about lung function using hyperpolarized noble gas MRI. Hyperpolarization is a technique which increases the normally weak MRI signal of gases such as helium or xenon roughly 100,000-fold. Inhaling a hyperpolarized gas provides a very strong signal source from within the lung that can be exploited to collect structural and functional information about the lung.

Of particular interest to me is the use of hyperpolarized xenon-129, which, unlike hyperpolarized helium, dissolves in significant quantities in both the lung tissue and blood. My research traces the xenon gas exchange and subsequent distribution in the body by the blood stream on a millisecond timescale. I am thereby able to design novel MR measurements which might allow the detection of lung disease at a much earlier stage than is possible with existing clinical modalities, as well as the monitoring of physiological responses to treatment.

Several of my ongoing research projects take advantage of these capabilities:

1. Deformations of the spine or the chest wall in young children can result in impaired lung development and restricted physiological motion, impairing lung function. While surgical treatment options are available, there is currently no consensus on the optimal timing or method of intervention that has the highest likelihood of improving lung function. I am investigating these questions using hyperpolarized xenon MRI in animal models and pediatric scoliosis patients.

2. Lung transplantation carries a high risk of organ rejection within 5 years. The best chances of successful treatment exist at the early stages of the rejection process, but symptoms and metrics based on existing diagnostic tools are frequently ambiguous until the optimal treatment window has already closed. I am developing hyperpolarized xenon MRI techniques that detect subtle changes in lung function that are potentially associated with early rejection.

3. Chronic obstructive pulmonary disease (COPD) is predominantly caused by extended smoke inhalation, with high morbidity and mortality but a generally slow progression that can can span decades. However, a subgroup of affected subjects develops a particularly aggressive form of COPD characterized by rapidly declining lung function. I am investigating the use of hyperpolarized xenon MRI as a tool for identifying these high-risk patients before irreparable lung damage has occurred and pharmacologic treatments still have the highest chances for success
Shampa Chatterjee
Associate Professor
Email Shampa Chatterjee
215-898-9101

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Shampa Chatterjee
Associate Professor
shampac@pennmedicine.upenn.edu
215-898-9101

Endothelial cells that line blood vessels. are continuously exposed to mechanical forces from blood flow and chemical stimuli from our environment. Irrespective of whether these are externally applied or arising from physiological “events”, these stimuli trigger changes in intracellular biochemical signaling and gene expression, eventually leading to cell differentiation, migration and apoptosis.

A major focus of my research is toward understanding endothelial responses that initiate and amplify inflammation. To achieve this, we employ in vitro, in situ an din vivo models of inflammation. Inflammation is simulated in my lab by 1) an in vitro flow adapted pulmonary endothelial cell network model 2) an in vivo mouse model of intratracheal endotoxin instillation 3) an in situ mouse lung ischemia reperfusion model and 4) clinical studies on e-cig smokers. For periodontal inflammation studies, we have developed an endotoxin exposed 3 D in vitro gum model. Our overall plan is employ these models to interrogate the role of inflammation signaling pathways in injury, so as to enable the design of interventional strategies to mitigate tissue damage.

Graduate Students

Mostafa Ismail
Doctoral Student
Email Mostafa Ismail
215-662-6671

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Mostafa Ismail
Doctoral Student
mostafai@seas.upenn.edu
215-662-6671

Research Interests
- Dynamic CT and MR imaging acquisition and analysis for studying and early detection of pulmonary disorders and studying lung mechanics.
- Improving CT and MR reconstruction binning and image quality.
- Study of lung metabolism with NMR spectroscopy.
Current Projects
- Using longitudinal dynamic CT imaging to studying lung dynamics and graft rejection in rat models of allogeneic and syngeneic unilateral lung transplant.
- Improving 4DCT image reconstruction for free-breathing rats.
- Developing software for fast and automated lung segmentation for large CT image datasets.
Luis Loza
Doctoral Student
Email Luis Loza
215-662-2283

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Luis Loza
Doctoral Student
LuisLoza@pennmedicine.upenn.edu
215-662-2283

Research Interests

My research interest lies in the development of MRI pulse sequences and their application for hyperpolarized 129Xe imaging in pre-clinical animal models. More specifically, I am interested in developing more robust, streamlined imaging techniques capable of capturing key aspects of lung function, such as ventilation and gas exchange, in the context of various pulmonary diseases, including radiation-induced lung injury and lung transplant rejection.

My current research focuses on investigating the minute differences in fractional ventilation measurements derived using three distinct imaging techniques in rodents: the well-established wash-in/wash-out, multi-flip-angle, and dynamic imaging.

I am also involved with our lab’s ongoing work developing a more pre-clinical robust xenon-transfer contrast (XTC) imaging protocol by optimizing imaging parameters (e.g., RF power, pulse timing and duration, etc.) in order to better distinguish between 129Xe dissolved in pulmonary tissue and red blood cells. The ultimate goal is to apply this optimized imaging technique to a murine model of lung transplantation in order to diagnose and characterize acute and chronic lung rejection processes
Hooman Hamedani
Doctoral Student
Email Hooman Hamedani
215-662-2283

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Hooman Hamedani
Doctoral Student
hooman@upenn.edu
215-662-2283

RESEARCH INTERESTS
- Multibreath imaging using hyperpolarized gas agents to regionally assess lung ventilation and gas exchange
- Design and fabrication of a high-precision gas mixing and administration device
- Development of breathing and imaging protocols for simultaneous measurement of multiple lung function parameters
- Dynamic imaging of the lung during normal breathing
- Using multiparametric response maps to assess lung function
- Developing deformable registration tools specific to lungs
- Early diagnosis of lung function deterioration and monitoring of functional response to treatment
CURRENT PROJECTS
- Estimating healthy ventilation nonuniformity
- Fabrication of a purely mechanical gas administration device capable of dosimetry
- Imaging of regional high-resolution fractional ventilation in human lungs during normal breathing
- Studying the effect of gas density and tidal volume on ventilation heterogeneity
- Comparison of imaging and non-imaging evaluations of the respiratory system
- Dynamic imaging of lung ventilation during normal breathing and nonrigid registration
- Registration of hyperpolarized gas MR images to chest CT scans for lobar segmentation
- Monitoring the response to endobronchial valve treatment for end-stage COPD
- Early detection of chronic rejection after lung transplantation
- Using a combination of hyperpolarized lung function maps and chest CT scans to target radiation therapy for lung cancer to less functional parts of the lung
- Early detection of lung function deterioration in COPD patients
- Ex vivo imaging of lung function
Jiawei Chen
Doctoral Student
Email Jiawei Chen
215-662-6671

Jiawei Chen
Doctoral Student
jiawchen@seas.upenn.edu
215-662-6671

Staff

Harrilla Profka
Research Specialist
Email Harrilla Profka
215-662-6671

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Harrilla Profka
Research Specialist
harilla.profka@uphs.upenn.edu
215-662-6671
- 15 years as veterinary practitioner with large animals
- 8 years experience in Cardiology/Radiology research at Upenn with pigs, sheep, rabbits, rats and mice
Ian Duncan
Grant Coordinator
Email Ian Duncan

Ian Duncan
Grant Coordinator
iand@pennmedicine.upenn.edu