Current Research

The long-term goal of the group is to improve the clinical outcomes and response rates for patients by using advanced dosimetry calculations and developing patient-specific treatment plans with 90Y-microsphere radioembolization therapy. 

Our lab uses quantitative imaging (99mTc-MAA SPECT/CT, 90Y SPECT/CT, 90Y PET/CT) to perform advanced patient-specific dosimetry and compute voxel-level absorbed dose estimates to tumors and normal liver. 

We are conducting clinical trials and have several funded research grants in this area. We work as part of a multi-disciplinary and multi-institutional team that includes Interventional Radiologists (A.M.), Medical Oncologists (A.K.), and Nuclear Medicine Physicians (M.L.). 

Key Participants and Collaborators: 
Armeen Mahvash, MD; Ahmed Kaseb, MD; Marnix Lam, MD, PhD

Clinical Studies:

• NCT03896646: A prospective single-center clinical trial RAPY90D: Radioembolization for HCC Patients with Personalized Yttrium-90 Dosimetry for Curative Intent (PIs: A.M. and S.C.K.)
•  NCT04736121: A prospective, multicenter, open-label, single-arm clinical trial design to evaluate the safety and efficacy of 90Y resin microspheres for the treatment of unresectable HCC: the DOORwaY90 study (PIs: A.M. and S.C.K.)
• Two additional studies are in the pipeline
  

Select References:

1. Mahvash A, et al. A prospective, multicenter, open-label, single-arm clinical trial design to evaluate the safety and efficacy of 90Y resin microspheres for the treatment of unresectable HCC: the DOORwaY90 (Duration Of Objective Response with arterial Ytrrium-90. BMC Gastroenterol 2022. DOI: 10.1186/s12876-022-02204-1 

2. Teyatteti A, et al. Disease control and failure patterns of unresectable hepatocellular carcinoma following transarterial radioembolization with yttrium-90 microspheres and with/without sorafenib. World J Gastroenterol 2021. DOI: 10.3748/wjg.v27.i47.8166

3. Levillain H, et al. International recommendations for personalized selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres. Eur J Nucl Med Mol Imaging 2021. DOI: 10.1007/s00259-020-05163-5

4. Salem R, et al. Clinical and dosimetric considerations for Y90: recommendations from an international multidisciplinary working group. Eur J Nucl Med Mol Imaging 2019. DOI: 10.1007/s00259-019-04340-5

5. Kappadath SC, et al. Hepatocellular carcinoma tumor dose response following 90Y-radioembolization with glass microspheres using 90YSPECT/CT based voxel dosimetry. Int J Radiation Oncol Biol Phys 2018.

6. Bastiaannet R, et al. The physics of radioembolization. EJNMMI Phys 2018.

7.  Balagopal A, et al. Characterization of 90Y-SPECT/CT self-calibration approaches on the quantification of voxel-level absorbed doses following 90Y-microsphere selective internal radiation therapy. Med Phys 2018.

8. Siman W, et al. Practical reconstruction protocol for quantitative 90Y bremsstrahlung SPECT/CT. Med Phys 2016.

We are evaluating deterministic (Grid-Based Boltzmann Solver) methods of radiation transport for fast and accurate patient-specific dosimetry calculations in targeted radionuclide therapies for nuclear medicine.  We have performed the fundamental work of implementing and validating GBBS for photons and beta emission used in nuclear medicine. We are currently adapting this approach for patient-specific imaging and dosimetry.

We have also investigated various voxel-dosimetry calculation techniques (Monte Carlo DOSXYZnrc, kernel-based, local deposition, etc.). We are investigating their dosimetric implications in 90Y microsphere therapy in the liver, lung, and in the liver/lung interface.

Key Participants and Collaborators: 
Justin K. Mikell, PhD; Firas Mourtada, Ph.D., Todd Wareing Ph.D.

Molecular Breast Imaging (MBI) is a breast-specific nuclear medicine imaging technique that uses a small field-of-view dual-headed semiconductor-based gamma camera in a mammographic configuration specifically designed to obtain high resolution planar images of 99mTc-sestamibi uptake throughout the breast.

We are using Monte Carlo simulations to develop novel acquisition and quantification techniques using existing clinical MBI technology to accurately measure absolute 99mTc-sestamibi uptake in tumors and normal breast tissue. We are actively working with our Breast Imaging Radiology colleagues to investigate the clinical role of quantitative MBI alongside standard of care imaging, with particular interest in using our quantitative measurements to aid in the early prediction of breast tumor response to neoadjuvant chemotherapy. 

Key Participants and Collaborators:
Benjamin P. Lopez, PhD; Beatriz Adrada, MD; Gaiane M. Rauch, M.D., Ph.D.

Select Publications (see Publication for expanded list):

• Lopez BP, et al. Functional tumor diameter measurement with Molecular Breast Imaging: Development and clinical application. Biomed Phys Eng Express 2022. DOI: 10.1088/2057-1976/ac85f0 
• Lopez BP, et al. Monte Carlo simulation of pixelated CZT detector with Geant4: validation of clinical molecular breast imaging system. Phys Med Biol 2021. DOI: 10.1088/1361-6560/ac0588

Our lab is actively engaged in exploring and improving clinical quantitative imaging. Some applications include:

• Comprehensive evaluation of material decomposition with rapid kVpswitching dual-energy CT scanners and its use for assessing bone mineral density. 
• Development of novel imaging processing algorithms to establish voxelbased bounds on activity concentration measurements in PET and SPECT imaging. This information helps overcome the inaccuracies resulting from the poor spatial resolution (relative to CT) and benefits clinical interpretation of PET/CT and SPECT/CT exams.
• Study of the effects of finite spatial resolution and system calibration on the quantitative accuracy of PET/CT and SPECT/CT using GATE Monte Carlo simulation.
• Evaluation of the effects of respiratory motion and associated motion compensation techniques during clinical PET/CT and SPECT/CT data acquisition on the accuracy of patient-specific dosimetry calculations.