Translational Engineering in Cancer Program Activities and Selected Scientific Reports
Keith Paulsen, PhD and Brian Pogue, PhD lead Translational Engineering in Cancer, which is one of four foundational Research Programs at Norris Cotton Cancer Center. They meet monthly to exchange findings and discuss new areas of interest. The Program has many additional activities to enhance the advancement of science in cancer imaging and radiobiology. Of the 22 members, most come from Dartmouth’s Thayer School of Engineering. at Dartmouth, and a significant number have their primary appointments through translational departments at the Geisel School of Medicine.
Translational Engineering in Cancer sponsors regular programs including the Translational Engineering in Cancer Seminar Series.
Focus groups are well-attended and the areas of interest are Innovative Surgical Devices and Methods, Radiation Therapy Dosimetry and Tumor Oximetry, as well as Cellular and Molecular Sensing Methods. Program-led symposia have included the annual meeting of electrical impedance community, which was supported by Cancer Center funding, and an annual Molecular-Guided Surgery conference in San Francisco, led by Dr’s Pogue and Paulsen as organizers.
At Dartmouth, opportunities for academic dialogue abound and members of Translational Engineering in Cancer are regular contributors. They participate in Norris Cotton Cancer Center Grand Rounds, the Imaging Medicine Summer Seminar Series, and the Biomedical Engineering Seminar Series.
Translational Engineering in Cancer’s presence in the clinical sphere is broad and significant including participation in Norris Cotton Cancer Center Tumor Boards held at Dartmouth-Hitchcock Medical Center in Lebanon, NH.
The Center for Imaging Medicine funds pilot collaborative studies with other institutions. Recruitment has been targeted collaboratively with Thayer, to attract Assistant Professor Geoffrey Luke, with expertise in ultrasound and photoacoustics, providing a new area of expertise to the TEC group. Additionally, several research assistant professor positions have been funded by R01 grants and maintain dedicated laboratory space in Williamson and Borwell, focused around the themes of surgical innovation.
TEC has fostered, and its members have embraced, the entrepreneurial culture at Dartmouth and as part of the NCCC’s most recent strategic plan. Specifically, TEC members are founders of 5 new start up ventures including CairnSurgical (Barth), DoseOptics (Pogue), InSight Surgical (Roberts), Rytek Medical (Halter), Lodestone Biomedical (Diamond), since the prior review, among others, and two of them (CairnSurgical and DoseOptics) have ongoing multi-center trials of new technologies emerging through TEC, and others are planned in the near future. Additionally, participation in a technology driven ACRIN trial was completed in this last cycle by members Paulsen, Pogue, Jiang, Kaufman, leading to key publication (B. J. Tromberg et al, Cancer Res, 2016). Finally, research programs have now impacted standard clinical care, through the recent 2016 FDA clearance of Fluorescence guided neurosurgery for glioma with Gleolan, an area where the TEC has consistently held a national leadership role under Roberts & Paulsen, and the team continues to push the boundaries of molecular guided surgery through establishment of multiple phase 0 trials for a Dartmouth-generated agent, which involves a wide section of the TEC investigators.
Mentoring is a top priority and Brian Pogue and Keith Paulsen both mentor Jonathan Elliott resulting in a recent K99 funding.
Translational Engineering in Cancer members are active teaching faculty and responsible for the following courses, among others:
- Brian Pogue - Medical Imaging, Biomedical Radiation Transport
- Keith Paulsen - Medical Device Development, Surgical Innovation
- Alex Hartov - Medical Image Processing
- P. Jack Hoopes, DVM, PhD - Introduction to Biomedical Engineering, Radiobiology
- Ryan Halter, PhD - Intermediate Biomedical Engineering
- John Weaver – Radiobiology
- Ben Williams – Radiation dosimetry & protection
- Colleen Fox – Radiation Therapy Physics
- David Gladstone – Medical Physics Practicum
- Michael Jermyn – Medical Image Visualization
Nationally, Translational Engineering in Cancer members participate in study sections including Brian Pogue who has chaired the Radiation Biology & Therapeutics conflict panel as well as a P41 review panel, Keith Paulsen who has chaired NCI’s Academic-Industrial Partnership Program Study Section and is ad hoc on several other panels. Harold Swartz is active in a number of national advisory boards including chairing the Advisory Committee for the Center for In Vivo Physiology at the University of Chicago (P41), chairing the Advisory Committee for the Neurosciences Center at the University of New Mexico (P30), and as a member of the Advisory Committee for the National Biomedical ESR Center at the University of Chicago (P41).
2014-2018 Selected Scientific Accomplishments
Key publications mark milestones of the TEC members, including these special highlights:
Barth RJ, Jr., Krishnaswamy V, Paulsen KD, Rooney TB, Wells WA, Rizzo E, Angeles CV, Marotti JD, Zuurbier RA, Black CC (2017). A Patient-specific 3D-printed form accurately transfers supine MRI-derived tumor localization information to guide breast-conserving surgery. Ann Surg Oncol 24(10):2950-2956. PMCID: PMC6015768
This paper reported on the origination of a tumor locating device for supine imaging to accompany regular breast lumpectomy surgery. The results led to a spin off company, Cairn Medical, founded by three members.
Caston RM, Schreiber W, Hou H, Williams BB, Chen EY, Schaner PE, Jarvis LA, Flood AB, Petryakov SV, Kmiec MM, Kuppusamy P, Swartz HM (2017). Development of the implantable resonator system for clinical EPR oximetry. Cell Biochem Biophys 75(3-4):275-283. PMCID: PMC5972368
This paper was foundational in demonstrating the in vivo oxygenation measurements could be acquired from tissue with an electron paramagnetic resonator that was physically inside the body. The EPR group at Dartmouth has a decades long history of pioneering this technology, and this opens up the potential to measure these signals from deeper into the body.
Ficko BW, NDong C, Giacometti P, Griswold KE, Diamond SG (2017). A feasibility study of nonlinear spectroscopic measurement of magnetic nanoparticles targeted to cancer cells. IEEE Trans Biomed Eng 64(5):972-979. PMCID: PMC5182167
This work demonstrated a fundamentally new way to sense binding to cancer cells with antibody coated magnetic nanoparticles.
Hao N, Nie Y, Shen T, Zhang JXJ (2018). Microfluidics-enabled rational design of immunomagnetic nanomaterials and their shape effect on liquid biopsy. Lab Chip 18(14):1997-2002.
Tadimety A, Closson A, Li C, Yi S, Shen T, Zhang JXJ (2018). Advances in liquid biopsy on-chip for cancer management: Technologies, biomarkers, and clinical analysis. Crit Rev Clin Lab Sci:1-23.
This nanotechnology development allows immunosensing via shaped nanomaterials in liquid biopsy specimens. The methods to enrich the samples and better sense minute concentrations of cancer specific analytes are a research focus which is ongoing.
Hill MV, Beeman JL, Jhala K, Holubar SD, Rosenkranz KM, Barth RJ, Jr. (2017). Relationship of breast MRI to recurrence rates in patients undergoing breast-conservation treatment. Breast Cancer Res Treat 163(3):615-622.
Reviewing the current status of breast conserving surgery, Dr Barth and colleagues found that recurrence was significantly reduced by the use of breast MRI.
Hoopes PJ, Wagner RJ, Duval K, Kang K, Gladstone DJ, Moodie KL, Crary-Burney M, Ariaspulido H, Veliz FA, Steinmetz NF, Fiering SN (2018, In press). Treatment of canine oral melanoma with nanotechnology-based immunotherapy and radiation. Mol Pharm. PMCID: PMC Journal - In Process
This seminal study reported on the first series of translational veterinary treatments for melanoma, using a pioneering approach to enhance immunotherapy with an engineered virus vector delivery.
Hou H, Khan N, Gohain S, Kuppusamy ML, Kuppusamy P (2018). Pre-clinical evaluation of OxyChip for long-term EPR oximetry. Biomed Microdevices 20(2):29.
This study presented the first long term oximetry tool for measurement at a single site repeatedly over many days. It follows many years of development for in situ oxygen measurement, and pioneered the path towards the eventual ongoing human trial, funded by an NCI P01 grant.
Leproux A, O'Sullivan TD, Cerussi A, Durkin A, Hill B, Hylton N, Yodh AG, Carp SA, Boas D, Jiang S, Paulsen KD, Pogue B, Roblyer D, Yang W, Tromberg BJ (2017). Performance assessment of diffuse optical spectroscopic imaging instruments in a 2-year multicenter breast cancer trial. J Biomed Opt 22(12):121604. PMCID: PMC5995138
As part of an ACRIN sponsored clinical trial, TEC investigators collaborated with several other cancer centers to complete evaluation of a new optical technology to monitor breast tumors while the patients are in neoadjuvant chemotherapy.
McClatchy III DM, Rizzo EJ, Meganck J, Kempner J, Vicory J, Wells WA, Paulsen KD, Pogue BW (2017). Calibration and analysis of a multimodal micro-CT and structured light imaging system for the evaluation of excised breast tissue. Phys Med Biol 62(23):8983-9000. PMCID: PMC5729028
This project reported on an Academic-Industry collaboration between PerkinElmer and Dartmouth to advance and test a hybrid imaging system that combines x-ray tomography with optical high spatial frequency scanning, for analysis of the resected margins in breast conserving surgery.
Murphy EK, Mahara A, Khan S, Hyams ES, Schned AR, Pettus J, Halter RJ (2017). Comparative study of separation between ex vivo prostatic malignant and benign tissue using electrical impedance spectroscopy and electrical impedance tomography. Physiol Meas 38(6):1242-1261. PMCID: PMC5757237
Murphy EK, Wu X, Halter RJ (2018). Fused-data transrectal EIT for prostate cancer imaging. Physiol Meas 39(5):054005.
These two papers form the basis of demonstrating that electrical impedance spectroscopy and tomography have diagnostic value in prostate surgical tissue evaluation.
Pogue BW, Zhu TC, Ntziachristos V, Paulsen KD, Wilson BC, Pfefer J, Nordstrom RJ, Litorja M, Wabnitz H, Chen Y, Gioux S, Tromberg BJ, Yodh AG (2018). Fluorescence-guided surgery and intervention - an AAPM emerging technology blue paper. Med Phys 45(6):2681-2688. PMCID: PMC Journal - In Process
In this study, Drs Pogue and Paulsen led an international task force in analyzing the needs for fluorescence guided resection surgery, and are setting goals for a professional society guidance report.
Roberts DW, Olson J (2017). Fluorescein guidance in glioblastoma resection. N Engl J Med 376(18):e36. PMCID: PMC5664222
In this study, Dr Roberts reported on the stunning visualization of a glioblastoma border with injection and timed visualization of fluorescein.
Samkoe KS, Bates BD, Elliott JT, LaRochelle E, Gunn JR, Marra K, Feldwisch J, Ramkumar DB, Bauer DF, Paulsen KD, Pogue BW, Henderson ER (2018). Application of fluorescence-guided surgery to subsurface cancers requiring wide local excision: Literature review and novel developments toward indirect visualization. Cancer Control 25(1):1-11. PMCID: PMC5933571
In this collaborative project the engineering and orthopaedic surgery teams combined to examine how fluorescence guided surgery could be used in sarcoma resection. This work led to independent funding for Dr Henderson to further pursue this in early evaluation of this as a surgical approach.
Pogue, BW, Feng, J, LaRochelle, EP, Bruža, P, Lin, H, Zhang, R, Shell, JR, Dehghani, H, Davis, SC, Vinogradov, SA, Gladstone, DJ, Jarvis, LA. (2018) Maps of in vivo oxygen pressure with submillimetre resolution and nanomolar sensitivity enabled by Cherenkov-excited luminescence scanned imaging. Nature Biomedical Engineering 2: 254–264 (2018) NIHM SID 950702
The development of Cherenkov light-based imaging of tissue has been a revolutionary way to image molecular probes in mice and rats at high spatial resolution. This demonstration outlined the technical limitations and potential for this method to sense oxygen in tumors during radiation therapy.