Preclinical longitudinal imaging of tumor microvascular radiobiological response with functional optical coherence tomography

Abstract

Radiation therapy (RT) is widely used for cancer treatment, alone or in combination with other therapies. Recent RT advances have revived interest in delivering higher dose in fewer fractions, which may invoke both cellular and microvascular damage mechanisms. Microvasculature may thus be a potentially sensitive functional biomarker of RT early response, especially for such emerging RT treatments. However it is difficult to measure directly and non-invasively, and its time course, dose dependencies, and overall importance in tumor control are unclear. We use functional optical coherence tomography for quantitative longitudinal in vivo imaging in preclinical models of human tumor xenografts subjected to 10, 20 and 30 Gy doses, furnishing a detailed assessment of vascular remodeling following RT. Immediate (minutes to tens of minutes) and early (days to weeks) RT responses of microvascular supply, as well as tumor volume and fluorescence intensity, were quantified and demonstrated robust and complex temporal dose-dependent behaviors. The findings were compared to theoretical models proposed in the literature.

Feasibility of using optical coherence tomography to detect acute radiation-induced esophageal damage in small animal models

“…[39][40][41] Esophageal OCT has been used to detect Barrett's esophagus in various studies. 20,40,42,43 Some studies used functional OCT microvascular imaging for radiobiological monitoring of different radiation dose levels in pancreatic human tumor xenografts 47 and in head and neck cancer using multifunctional OCT in a clinical pilot study in patients. 48 Moreover, there are pilot patient studies reported on using microvascular OCT imaging with developed oral imaging probes to monitor late oral radiation-induced damages in vivo.…”

Preclinical quantitative in-vivo assessment of skin tissue vascularity in radiation-induced fibrosis with optical coherence tomography

“…35 Although single dose of 40 Gy is not clinically used (cumulative dose ranges between 50 and 70 Gy, fractionated over 5 to 7 weeks), it was considered appropriate to simulate severe radiation injury and achieve RIF with telangiectasia in mice within first 6 months after treatment, based on previous preclinical experience. 36,37 A swept-source OCT system based on a quadrature interferometer to suppress the complex conjugate artifact 38,39 was used in this study [ 110 nm and an average output power of 10 mW. The axial and lateral resolutions in air were 8 and 15 μm, respectively.…”

STE20/PAKA Protein Kinase Gene Releases an Autoinhibitory Domain through Pre-mRNA Alternative Splicing in the Dermatophyte Trichophyton rubrum

“…Recently, using the same RNA-Seq data of the present work, our group published AS events in a T. rubrum strain. An IR event was presented in the gene encoding the enzyme inosine monophosphate dehydrogenase (IMPDH; TERG_06846), which is involved in purine biosynthesis, as confirmed by qRT-PCR [ 41 ]. However, in this case, and in most circumstances described in fungi, the IR process generated an altered reading frame code and, consequently, smaller proteins with disrupted functional domains.…”

“…T. rubrum strain CBS 118892, obtained from the Centraalbureau voor Schimmelcultures in the Netherlands, was cultured as previously described [ 41 ]. All assays were carried out in triplicate.…”