Georges El Fakhri

Center for Advanced Radiological Sciences
Department of Radiology
Massachusetts General Hospital
55 Fruit Street
Boston, MA 02114

tel: (617) 726-9640; fax: (617) 726-6165
email: elfakhri@pet.mgh.harvard.edu
web: http://nmmiweb.mgh.harvard.edu/cars/index.html

Research Interests and Goals:

Mission: The Center for Advanced Radiological Sciences (CARS) mission is the development of new medical imaging technologies and their application in research and clinical settings. It focuses on advanced quantitative medical imaging using modalities such as positron emission tomography, computed tomography (PET-CT) and magnetic resonance (PET-MR) for neurological, oncologic and cardiac explorations. CARS is home to about 50 faculty, staff, post-doctoral fellows and graduate students, and is based in the Radiology Department of Massachusetts General Hospital, Harvard Medical School.

Adaptive Proton Therapy Using in-room PET
The goal of this research is to develop a novel approach for adaptive in-room Positron Emission Tomography (PET) monitoring of Proton Beam Therapy using endogenously generated positrons. Verification of the beam delivery within the patient is very important to ensure the proper functioning of treatment planning and delivery systems.  A full-ring PET-CT scanner within the treatment room is very desirable so that the patient can be imaged on the same bed immediately after irradiation.  We are investigating the potential of in-room PET-CT monitoring/verification for proton therapy using a mobile full-ring prototype PET-CT scanner recently available at MGH.

Quantitative Simultaneous PET-MRI  
The goals of this research are to develop novel quantitative methods for simultaneous whole-body (WB) PET-MR imaging, validate these methods in animal models and evaluate their clinical value, compared to PET-CT, in monitoring response to cancer therapy. Simultaneous PET-MR is a novel and promising imaging modality that is generating substantial interest in the medical community and offers the scientific community many challenges and opportunities. Unlike sequentially-acquired WB PET-CT scans, the simultaneous acquisition of MR and PET data can be used to incorporate MR information into the PET reconstruction model.  We hypothesize that the additional MR information will yield substantial improvement of PET in terms of lesion detection and activity estimation.

Simultaneous Dual Isotope SPECT and PET
We are bringing to fruition our successful developments of accurate compensation methods for physical factors affecting image quality and reconstruction approaches for quantitative dual-isotope SPECT, and are expanding our scope to PET.  We are presently evaluating the performance of two novel scatter correction methods for quantitative single and dual-isotope PET that we have developed.  We are also extending our previous work in SPECT to novel approaches to dual-isotope dynamic brain PET using spatio-temporal information.  We are assessing the performance of quantitative dual-isotope SPECT and PET in activity estimation tasks related to early diagnosis and quantitation of disease extent in coronary artery disease (CAD) and early Parkinson disease (PD) with or without dementia.

Quantitative Y-86 PET for Personalized Radionuclide Therapy
Targeted radionuclide therapy (TRT) and radioimmunotherapy (RIT) are at the forefront of molecular cancer treatment modalities that involve the use of cancer cell-targeting radiopharmaceuticals, such as radiolabeled antibodies.  Y-90 based therapy has thus far been hampered by the inability to accurately image and quantify the distribution of Y-90 within the body as the latter is a pure β emitter.  Quantitative Y-86 PET imaging allows personalized patient treatment by enabling tailored Y-90 TRT based on the quantitative biodistribution of Y-86 uptake but presents unique challenges as it requires compensation for many physical effects including gamma cascade that greatly affect image quality and accuracy.  We are accurately modeling the physics of PET imaging using isotopes with cascade gammas, and developing correction algorithms to achieve quantitative Y-86 PET dosimetry.

Absolute Quantitation of Myocardial Blood Flow Using Dynamic Rb-82 PET  
The central hypothesis of this proposal is that objective quantitation of myocardial perfusion and coronary flow reserve can be achieved using 82Rb imaging and, furthermore, that these measures are important determinants of clinical risk and, thus, useful for optimizing management decisions in patients with coronary artery disease (CAD).  We use dynamic 82Rb PET along with innovative approaches based on generalized factor analysis of dynamic sequences (GFADS), that allow automatic estimation of left and right ventricle input functions, as well as region based compartment analysis to characterize and quantify the coronary flow reserve (CFR) as well as the severity and extent of perfusion abnormalities that occur in CAD.

Objective Assessment of Image Quality for Estimation and Detection Tasks 
We are developing a rigorous evaluation methodology for objective assessment of image quality for lesion detection and activity quantitation tasks. We have applied our methods to assess the performance of different acquisition (2D vs 3D) and processing methods for variable patient sizes in the context of lesion detection in whole body FDG-PET. Our results show that for lesion detection and activity quantitation tasks, 3D imaging yielded better lesion detectability than 2D (p<0.025, two-tailed paired t-test) in patients of normal size (Body Mass Index [BMI]< 31). However 2D imaging yielded better lesion detectability than 3D in large patients (BMI > 31) as 3D performance deteriorated in large patients (p<0.05). 2D and 3D yielded similar results for different lesion sizes. We have extended our work to the assessment of performance of Time of Flight PET and determined the gains that can be achieved in lung and liver cancer for lesion detection tasks in a cohort of 100 patients in collaboration with Dr. Karp's lab at UPENN.

 

Selected Publications:

El Fakhri, G., Surti, S., Trott, C.M., Scheuermann, J., Karp, J.S. Improvement in Lesion Detection with Whole–Body Oncologic TOF - PET. J. Nucl. Med. 2011; 52: 347-353.

Guérin, B. and El Fakhri, G. Novel scatter compensation of list-mode PET data using spatial and energy dependent corrections. IEEE Trans. Med. Imag. 2011; 30: 759-773.

España, S., Zhu, X., Daartz, J., El Fakhri, G., Bortfeld, T., Paganetti, H. Reliability of proton-nuclear interaction cross section data to predict proton-induced PET images in proton therapy.  Phys. Med. Biol. 2011; 56:2687-2698.

Guérin, B., Reese, T., Cho, S., Chun, S.Y., Zhu, X., Catana, C., Alpert, N.M., El Fakhri, G. Non-rigid PET motion compensation using tagged-MRI in simultaneous PET-MR imaging.  Med. Phys. 2011; 38: 3025-3038.

Zhu, X, España, S.,  Daartz, J., Liebsch, N., Ouyang, J., Paganetti, H., Bortfeld, T., El Fakhri, G.  Proton beam range verification with in-room PET imaging. Phys. Med. Biol. 2011; 56: 4041-4054.

Chun, S.Y., Reese, T., Guerin, B., Catana, C., Zhu, X., Alpert, N., El Fakhri, G.  Tagged MR-based Motion Correction in Simultaneous PET-MR. J. Nucl. Med. 2012; 1284-1291 (Featured cover article).

Alpert, N., Fang, D., and El Fakhri, G.  Single-scan Rest/Stress Imaging 18F-labeled flow tracers – Theory and Simulation Studies.  Med. Phys. in press.

Fang, D., El Fakhri, G., Becker, A., and Alpert, N. Parametric imaging with Bayesian priors: A validation study with 11C-Altropane PET.  NeuroImage 2012;.61: 131-138.

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