Ashley R. Proctor

Non-contact scanning diffuse correlation tomography system for three-dimensional blood flow imaging in a murine bone graft model.

A non-contact galvanometer-based optical scanning system for diffuse correlation tomography was developed for monitoring bone graft healing in a murine femur model. A linear image reconstruction algorithm for diffuse correlation tomography was tested using finite-element method based simulated data and experimental data from a femur or a tube suspended in a homogeneous liquid phantom. Finally, the non-contact system was utilized to monitor in vivo blood flow changes prior to and one week after bone graft transplantation within murine femurs. Localized blood flow changes were observed in three mice, demonstrating a potential for quantification of longitudinal blood flow associated with bone graft healing.

Non-Invasive Monitoring of Temporal and Spatial Blood Flow during Bone Graft Healing Using Diffuse Correlation Spectroscopy

Vascular infiltration and associated alterations in microvascular blood flow are critical for complete bone graft healing. Therefore, real-time, longitudinal measurement of blood flow has the potential to successfully predict graft healing outcomes. Herein, we non-invasively measure longitudinal blood flow changes in bone autografts and allografts using diffuse correlation spectroscopy in a murine femoral segmental defect model. Blood flow was measured at several positions proximal and distal to the graft site before implantation and every week post-implantation for a total of 9 weeks (autograft n = 7 and allograft n = 10). Measurements of the ipsilateral leg with the graft were compared with those of the intact contralateral control leg. Both autografts and allografts exhibited an initial increase in blood flow followed by a gradual return to baseline levels. Blood flow elevation lasted up to 2 weeks in autografts, but this duration varied from 2 to 6 weeks in allografts depending on the spatial location of the measurement. Intact contralateral control leg blood flow remained at baseline levels throughout the 9 weeks in the autograft group; however, in the allograft group, blood flow followed a similar trend to the graft leg. Blood flow difference between the graft and contralateral legs (ΔrBF), a parameter defined to estimate graft-specific changes, was elevated at 1–2 weeks for the autograft group, and at 2–4 weeks for the allograft group at the proximal and the central locations. However, distal to the graft, the allograft group exhibited significantly greater ΔrBF than the autograft group at 3 weeks post-surgery (p < 0.05). These spatial and temporal differences in blood flow supports established trends of delayed healing in allografts versus autografts.

Non-invasive diffuse correlation tomography reveals spatial and temporal blood flow differences in murine bone grafting approaches

Longitudinal blood flow during murine bone graft healing was monitored non-invasively using diffuse correlation tomography. The system utilized spatially dense data from a scanning set-up, non-linear reconstruction, and micro-CT anatomical information. Weekly in vivo measurements were performed. Blood flow changes in autografts, which heal successfully, were localized to graft regions and consistent across mice. Poor healing allografts showed heterogeneous blood flow elevation and high inter-subject variabilities. Allografts with tissue-engineered periosteum showed responses intermediate to both autografts and allografts, consistent with healing observed. These findings suggest that spatiotemporal blood flow changes can be utilized to differentiate the degree of bone graft healing.

Chemotherapeutic drug-specific alteration of microvascular blood flow in murine breast cancer as measured by diffuse correlation spectroscopy

The non-invasive, in vivo measurement of microvascular blood flow has the potential to enhance breast cancer therapy monitoring. Here, longitudinal blood flow of 4T1 murine breast cancer (N=125) under chemotherapy was quantified with diffuse correlation spectroscopy based on layer models. Six different treatment regimens involving doxorubicin, cyclophosphamide, and paclitaxel at clinically relevant doses were investigated. Treatments with cyclophosphamide increased blood flow as early as 3 days after administration, whereas paclitaxel induced a transient blood flow decrease at 1 day after administration. Early blood flow changes correlated strongly with the treatment outcome and distinguished treated from untreated mice individually for effective treatments.

Temporal blood flow changes measured by diffuse correlation tomography predict murine femoral graft healing

Blood flow changes during bone graft healing have the potential to provide important information about graft success, as the nutrients, oxygen, circulating cells and growth factors essential for integration are delivered by blood. However, longitudinal monitoring of blood flow changes during graft healing has been a challenge due to limitations in current techniques. To this end, non-invasive diffuse correlation tomography (DCT) was investigated to enable longitudinal monitoring of three-dimensional blood flow changes in deep tissue. Specific to this study, longitudinal blood flow changes were utilized to predict healing outcomes of common interventions for massive bone defects using a common mouse femoral defect model. Weekly blood flow changes were non-invasively measured using a diffuse correlation tomography system for 9 weeks in three types of grafts: autografts (N = 7), allografts (N = 6) and tissue-engineered allografts (N = 6). Healing outcomes were quantified using an established torsion testing method 9 weeks after transplantation. Analysis of the spatial and temporal blood flow reveals that major differences among the three groups were captured in weeks 1–5 after graft transplantation. A multivariate model to predict maximum torque by relative blood flow changes over 5 weeks after graft transplantation was built using partial least squares regression. The results reveal lower bone strength correlates with greater cumulative blood flow over an extended period of time (i.e., 1–5 weeks). The current research demonstrates that DCT-measured blood flow changes after graft transplantation can be utilized to predict long-term healing outcomes in a mouse femoral graft model.

Diffuse correlation tomography reveals spatial and temporal difference in blood flow changes among murine femoral grafts

Diffuse correlation tomography was utilized to noninvasively monitor 3D blood flow changes in three types of healing mouse femoral grafts. Results reveal the spatial and temporal difference among the groups.

Non-contact scanning diffuse optical tomography for three-dimensional vascular imaging in a murine bone graft model

A non-contact scanning diffuse optical tomography system was developed for monitoring vascularization during bone graft healing in a murine femur model. Preliminary testing of the system using tissue phantoms is presented.

Monitoring blood flow changes induced by nicotinamide injection in mouse leg using diffuse correlation spectroscopy

Diffuse Correlation Spectroscopy was employed to monitor relative blood flow in mouse leg before and after injection of nicotinamide (1000 mg/kg). The result shows an average increase of 172% in relative blood flow, 30 minutes after injection.

Quantification of early hemodynamic changes induced by cyclophosphamide on breast cancer xenografts using diffuse optics

A significant difference between a treated and a control group of mice with breast cancer were observed in hemodynamic parameters quantified with diffuse optics at day 3 after cyclophosphamide treatment.