Experimental Radiobiology Research Group

Optical technologies for assessing biological response to radiotherapy

In radiation therapy, standard radiation doses have been empirically determined and are delivered without consideration of in vivo disease response. There exists no accepted imaging or serologic marker proven useful for assessing radio-response during the course of therapy. Our research program involves the investigation of Raman spectroscopic methods for understanding, predicting, and monitoring the response of biological systems to ionizing radiation that is typically used in radiotherapy. The program is a collaborative effort between physics, chemistry, biology, and engineering.

Research areas

Typical research areas include, but are not limited to:

  • Understanding cellular response to radiotherapy: Irradiated cell lines varying in inherent radiosensitivity and other biological parameters are interrogated using Raman spectroscopy, with the aim of observing and understanding the biological pathways that are responding to the radiation.
  • Murine models for observation of radio-response: In vitro tumour irradiations are performed and irradiated tumour is excised and analyzed using Raman spectroscopy. Results are correlated to in vitro models.
  • Automation of Raman acquisition techniques: We aim to utilize microfluidic systems to automate Raman acquisition of irradiated cells and tissues.
  • Raman analysis: We currently utilize Principal Component Analysis (PCA) for the analysis and identification of biological response present within the acquired data. Current investigations involve alternate methods of analysis with the aim of enhanced information extraction.
Representative Raman spectra of irradiated and unirradiated H460 cancer cells

(a) Representative Raman spectra of irradiated and unirradiated H460 cancer cells. Also shown are the difference spectrum, the Principal component (PC) corresponding to radiation damage, and a spectrum of pure glycogen.

(b) Principal component scores for radiation PC component for a range of cancer cell lines irradiated between 0 – 10 Gy and data acquired between 1 – 3 days post irradiation.

Cell survival chart

(c) Cell survival curves for the cell lines shown in (b).

Dose Tracking in Cervical Brachytherapy

The team has recently been investigating tracking the dose delivered to organs at risk over multiple fractions of treatment in cervical brachytherapy. 3D imaging has greatly improved the conformality of HDR brachytherapy. MRI imaging fused to planning CTs allows the actual tumour to be contoured and targeted and 3D CT imaging allows all neighbouring organs at risk (rectum, sigmoid, bladder, small bowel) to be monitored and spared as much as possible. HDR brachytherapy for cervix is delivered in 3-5 fractions and at the moment organ doses are assessed simply by summing the dose each gets each fraction. This assumes that the same portion of each organ is maximally irradiated each fraction. Using deformable images registration tools we can now track where the maximally irradiated portion of each organ actually is from fraction to fraction and determine what the true dose maximum dose to each organ is. This aids in understanding what organ doses are actually delivered and thereby may enhance our understanding of what dose levels correlate with normal tissue complications.

Improved Imaging for Gynaecological Brachytherapy

The brachytherapy team at CSI is committed though research and development to advancement of HDR brachytherapy treatments for gynaecological cancers.

One arena is improving image guidance for interstitial gynaecological brachytherapy. The team at CSI has pioneered an interstitial technique that mimics prostate brachytherapy by mounting an ultrasound probe and template on a prostate stepper and performing trans-vaginal ultrasound (US) imaging during needle implant. This is, however, still limiting due to the 2D nature of the intra-operative imaging, the variable visibility of the target on US, and the fact that we cannot image above the vaginal vault, restricting the number of patients we can treat with this technique. In collaboration with Dr Aaron Fenster of the Imaging Research Labs, Robarts Research Institute, London, Ontario, the team at CSI proposes to develop a system to fuse pre- operative magnetic resonance images (MRI) (where the target is fully visible) to 3D intra-operative US images. This technique will incorporate needle tracking technology allowing better assessment implant quality before imaging for planning. The possibility of combining different US modalities intra- operatively will also be explored; for instance, using both front-firing and side-firing transducers to image above the vault as well as along the length of the vagina. Incorporating Doppler imaging to better identify the target will also be explored.

Another arena for improved imaging in gynaecological brachytherapy is in visualization of the wall of the vagina, an often ignored organ at risk in gynaecological brachytherapy. Vaginal side effects have a large impact on patients’ quality of life following treatment and vaginal stenosis makes follow up exams difficult and painful. This group seeks to investigate a means of identifying the vaginal wall in imaging that can be routinely applied in the clinic. This will facilitate a retrospectively review of the doses delivered to the vaginal wall during treatment for cervix cancer and an investigation of any correlations between dose and complications. Further, we aim to develop a means of routinely prospectively monitoring vaginal wall dose.

Advancing Prostate Brachytherapy

The brachytherapy team at CSI is the only group in BC that offers HDR brachtherapy as a treatment option for prostate cancer. Research is clinically focused on improving HDR prostate treatment strategies and monitoring treatment dosimetry. Recent investigations include integrating a boost dose to the dominant intra-prostatic lesion into the ultrasound based planning and treatment approach used at CSI via “dose painting”.

Recent Publication Highlights

D Morton, D Batchelar, M Hilts, T Berrang and J Crook. Incorporating 3D ultrasound into permanent breast seed implant brachytherapy treatment planning. Brachytherapy Oct 2016.

D Morton, M Hilts, D Batchelar and J Crook. Seed placement in permanent breast seed implant brachytherapy: Are concerns over accuracy valid? IJROBP 95(3) 2016, pp1050-1057.

M Hilts, H Halperin, D Morton, D Batchelar, F Bachand, R Chowdhury, J Crook. Skin dose in breast brachytherapy: Defining a robust metric. Brachytherapy 14(6) 2015, pp970-978.

M Hilts, D Batchelar, J Rose and J Crook. Deformable image registration for defining the post implant seroma in permanent breast seed implant brachytherapy. Brachytherapy 14(3) 2015, pp409-418.

J Crook, A Ots, M Gaztanaga, M Schmid, C Araujo, M Hilts, D Batchelar, B Parker, F Bachand and MP Millette. Ultrasound-planned high-dose-rate prostate brachytherapy: Dose painting to the dominant intraprostatic lesion. Brachytherapy 13(5) 2014, pp433-441.