Towards detection of brain injury using multimodal non-invasive neuromonitoring in adults undergoing extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary bypass that provides life-saving support to critically ill patients whose illness is progressing despite maximal conventional support. Use in adults is expanding, however neurological injuries are common. Currently, the existing brain imaging tools are a snapshot in time and require high-risk patient transport. Here we assess the feasibility of measuring diffuse correlation spectroscopy, transcranial Doppler ultrasound, electroencephalography, and auditory brainstem responses at the bedside, and developing a cerebral autoregulation metric. We report preliminary results from two patients, demonstrating feasibility and laying the foundation for future studies monitoring neurological health during ECMO.

Spatial frequency domain imaging for the longitudinal monitoring of vascularization during mouse femoral graft healing.

Allograft is the current gold standard for treating critical-sized bone defects. However, allograft healing is usually compromised partially due to poor host-mediated vascularization. In the efforts towards developing new methods to enhance allograft healing, a non-terminal technique for monitoring the vascularization is needed in pre-clinical mouse models. In this study, we developed a non-invasive instrument based on spatial frequency domain imaging (SFDI) for longitudinal monitoring of the mouse femoral graft healing. SFDI technique provided total hemoglobin concentration (THC) and oxygen saturation (StO2) of the graft and the surrounding soft tissues. SFDI measurements were performed from 1 day before to 44 days after graft transplantation. Autograft, another type of bone graft with higher vascularization potential was also measured as a comparison to allograft. For both grafts, the overall temporal changes of the measured THC agreed with the physiological expectations of vascularization timeline during bone healing. A significantly greater increase in THC was observed in the autograft group compared to the allograft group, which agreed with the expectation that allografts have more compromised vascularization.

Longitudinal 3D Blood Flow Distribution Provided by Diffuse Correlation Tomography during Bone Healing in a Murine Fracture Model.

Noninvasive monitoring of vascularization can potentially diagnose impaired bone healing earlier than current radiographic methods. In this study, a noncontact diffuse correlation tomography (DCT) technique was employed to measure longitudinal blood flow changes during bone healing in a murine femoral fracture model. The three-dimensional distribution of the relative blood flow was quantified from one day pre-fracture to 48 days post-fracture. For three mice, frequent DCT measurements were performed every other day for one week after fracture, and then weekly thereafter. A decrease in blood flow was observed in the bone fracture region at one day post-fracture, followed by a monotonic increase in blood flow beyond the pre-injury baseline until five to seven days post-fracture. For the remaining 12 mice, only weekly DCT measurements were performed. Data collected on a weekly basis show the blood flow for most mice was elevated above baseline during the first two post-fracture weeks, followed by a subsequent decrease. Torsional strength of the excised femurs was measured for all 15 mice after 7 weeks of healing. A metric based on the early blood flow changes shows a statistically significant difference between the high strength group and the low strength group.

Validation of diffuse correlation spectroscopy sensitivity to nicotinamide-induced blood flow elevation in the murine hindlimb using the fluorescent microsphere technique.

Nicotinamide has been shown to affect blood flow in both tumor and normal tissues, including skeletal muscle. Intraperitoneal injection of nicotinamide was used as a simple intervention to test the sensitivity of noninvasive diffuse correlation spectroscopy (DCS) to changes in blood flow in the murine left quadriceps femoris skeletal muscle. DCS was then compared with the gold-standard fluorescent microsphere (FM) technique for validation. The nicotinamide dose-response experiment showed that relative blood flow measured by DCS increased following treatment with 500- and 1000-mg / kg nicotinamide. The DCS and FM technique comparison showed that blood flow index measured by DCS was correlated with FM counts quantified by image analysis. The results of this study show that DCS is sensitive to nicotinamide-induced blood flow elevation in the murine left quadriceps femoris. Additionally, the results of the comparison were consistent with similar studies in higher-order animal models, suggesting that mouse models can be effectively employed to investigate the utility of DCS for various blood flow measurement applications.