Sarcoma
Rahul Pal, PhD
Instructor
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown MA, United States
.jpg "Thinzar M. Lwin, MD (she/her/hers) photo")
Thinzar M. Lwin, MD (she/her/hers)
Assistant Professor
Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA, California, United States
Thinzar M. Lwin, MD (she/her/hers)
Assistant Professor
Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA, California, United States
Murali Krishnamoorthy, PhD
Post Doctorate Scholar
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown MA, United States
Hannah R. Collins, n/a
Research Staff
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown MA, United States
Corey D. Chan, MD
Post Doctorate Scholar
Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK, United States
Kurt R. Weiss, MD
Associate Professor of Surgery
Department of Orthopedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
Kenneth Rankin, MD
Professor of Surgery
Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK, United States
Santiago Lozano-Calderon, MD, PhD
Associate Professor of Surgery
Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston MA, United States
Anand TN Kumar, PhD
Associate Professor in Radiology
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown MA, United States
Complex surgeries are performed to resect sarcomas, but tissue discrimination at the time of resection is determined subjectively; by visual inspection, palpation, and clinical judgment. Unrecognized deposits of remaining tumors can lead to local recurrence and decreased survival. There is a vital need for an objective approach to enhance intraoperative tumor identification. Current approaches to intra-operative detection of fluorescence are based on the detection of fluorescence intensity and do not offer adequate contrast. We evaluate the detection of fluorescence lifetime (FLT) using indocyanine green (ICG) contrast to improve the sensitivity and accuracy of sarcoma identification.
Methods: We performed an IRB approved clinical study of 22 patients undergoing surgery for sarcomas who received ICG intravenously (0.5-1mg/kg) prior to surgery. Fresh and formalin fixed resection specimens from surgeries performed at MGH, University of Newcastle on Tyne, and UPMC were imaged. Wide-field imaging was performed using white light, fluorescence intensity, and time-domain (FLT) imaging. Slides underwent FLT microscopy (FLIM) and H&E staining. Histology images were annotated by pathologists blinded to fluorescence images. Tumor-normal tissue boundaries were identified. Distribution of fluorescence intensity and FLT were measured. Sensitivity, specificity, and ROC analyses were performed.
Results: Paired tumor and normal tissue data were available for 8/22 sarcoma patients. The average fluorescence intensity in the tumor was highly heterogeneous; in 3 patients, there was even a higher fluorescence in the normal tissue compared to the tumors (Figure 1B). Mean FLT in all tumors were significantly longer than the normal tissue FLT (Figure 1C). The sensitivity and specificity for ICG-FLT in detection of tumors was 94.2 ± 3.0% and 93.3 ± 2.2% (J = 86.1 ± 4.6%) respectively, with an accuracy of 97.1± 1.3% (Figure 1D). The sensitivity and specificity for standard fluorescence intensity imaging in detection of tumors was 62.7 ± 31.6% and 51.7 ± 12.1% (J = 32.4 ± 13.1%) respectively, with an accuracy of 54.4 ± 24.7%.
Conclusions: In patients who have received ICG prior to surgery, measurement of FLT demonstrated significantly longer lifetimes in sarcomas, compared to the surrounding normal tissues. While fluorescence intensity was able to highlight the tumor, FLT imaging had a higher sensitivity, specificity, and accuracy in delineating sarcomas. The work demonstrates a highly promising potential application of FLT for next-generation fluorescence-guided surgery.