Intraoperative detection of blood vessels with an imaging needle during neurosurgery in humans

Intracranial hemorrhage can be a devastating complication associated with needle biopsies of the brain. Hemorrhage can occur to vessels located adjacent to the biopsy needle as tissue is aspirated into the needle and removed. No intraoperative technology exists to reliably identify blood vessels that are at risk of damage. To address this problem, we developed an “imaging needle” that can visualize nearby blood vessels in real time. The imaging needle contains a miniaturized optical coherence tomography probe that allows differentiation of blood flow and tissue. In 11 patients, we were able to intraoperatively detect blood vessels (diameter, \u3e500 μm) with a sensitivity of 91.2% and a specificity of 97.7%. This is the first reported use of an optical coherence tomography needle probe in human brain in vivo. These results suggest that imaging needles may serve as a valuable tool in a range of neurosurgical needle interventions

Monitoring kidney optical properties during cold storage preservation with spatial frequency domain imaging.

Transplantation of kidneys results in delayed graft function in as many as 40% of cases. During the organ transplantation process, donor kidneys undergo a period of cold ischemic time (CIT), where the organ is preserved with a cold storage solution to maintain tissue viability. Some complications observed after grafting may be due to damage sustained to the kidney during CIT. However, the effects due to this damage are not apparent until well after transplant surgery has concluded. To this end, we have used spatial frequency domain imaging (SFDI) to measure spatially resolved optical properties of porcine kidneys over the course of 80-h CIT. During this time, we observed an increase in both reduced scattering (μs&') and absorption (μa) coefficients. The measured scattering b parameter increased until 24 h of CIT, then returned toward baseline during the remaining duration of the imaging sequence. These results show that the optical properties of kidney tissue change with increasing CIT and suggest that continued investigation into the application of SFDI to kidneys under CIT may lead to the development of a noninvasive method for assessing graft viability

Functional Ultrasound (fUS) During Awake Brain Surgery: The Clinical Potential of Intra-Operative Functional and Vascular Brain Mapping

Background and Purpose: Oncological neurosurgery relies heavily on making continuous, intra-operative tumor-brain delineations based on image-guidance. Limitations of currently available imaging techniques call for the development of real-time image-guided resection tools, which allow for reliable functional and anatomical information in an intra-operative setting. Functional ultrasound (fUS), is a new mobile neuro-imaging tool with unprecedented spatiotemporal resolution, which allows for the detection of small changes in blood dynamics that reflect changes in metabolic activity of activated neurons through neurovascular coupling. We have applied fUS during conventional awake brain surgery to determine its clinical potential for both intra-operative functional and vascular brain mapping, with the ultimate aim of achieving maximum safe tumor resection. Methods: During awake brain surgery, fUS was used to image tumor vasculature and task-evoked brain activation with electrocortical stimulation mapping (ESM) as a gold standard. For functional imaging, patients were presented with motor, language or visual tasks, while the probe was placed over (ESM-defined) functional brain areas. For tumor vascular imaging, tumor tissue (pre-resection) and tumor resection cavity (post-resection) were imaged by moving the hand-held probe along a continuous trajectory over the regions of interest. Results: A total of 10 patients were included, with predominantly intra-parenchymal frontal and temporal lobe tumors of both low and higher histopathological grades. fUS was able to detect (ESM-defined) functional areas deep inside the brain for a range of functional tasks including language processing. Brain tissue could be imaged at a spatial and temporal resolution of 300 μm and 1.5–2.0 ms respectively, revealing real-time tumor-specific, and healthy vascular characteristics. Conclusion: The current study presents the potential of applying fUS during awake brain surgery. We i

Laser speckle contrast imaging for intraoperative monitoring of cerebral blood flow

Ensuring adequate blood flow during surgical procedures is crucial, as prolonged ischemia can result in tissue death and lead to poor clinical outcomes. This is especially important during neurosurgery, since the brain relies on a constant supply of cerebral blood flow (CBF) to maintain normal function. Intraoperative blood flow monitoring tools are essential to detect ischemia in a timely manner, and allow surgical correction before the onset of irreversible brain injury. Laser speckle contrast imaging (LSCI) is an optical imaging method that provides blood flow maps with high spatiotemporal resolution, and overcomes many of the limitations of current intraoperative monitoring technologies. The objective of this dissertation is to demonstrate that LSCI is an effective tool for blood flow monitoring during neurosurgery, and to optimize and improve LSCI technology for clinical use. This research has two primary elements: assessing the LSCI instrumentation components in a controlled laboratory setting, and evaluating the clinical performance of LSCI during neurosurgery. The laboratory study aims to determine the optimal specifications for the clinical instrument design, using controlled static and microfluidic flow experiments. Two of the main components of the LSCI instrument are the camera used for recording, and the laser used for coherent illumination of the tissue. Thus, a broad camera and laser comparison was performed spanning a wide array of available hardware options to determine which specifications are the most important for reliable and highly sensitive flow measurements. The two-phase clinical study aims to demonstrate the performance and utility of LSCI in a neurosurgical setting as a potential tool for real-time, continuous, and noninvasive image guidance. These studies demonstrate that LSCI can produce blood flow maps consistent with expected physiological trends, and show the impact of instrument design and image acquisition techniques on image quality and quantitative flow assessment. The results from both the laboratory and clinical studies can be used to design a more sensitive and robust LSCI system, which increases its value as an intraoperative tool for monitoring blood flow. LSCI has the potential to be the next generation of neurosurgical image guidance for blood flow visualization, and the work presented in this dissertation can accelerate its clinical adoption.Biomedical Engineerin

NONINVASIVE MULTIMODAL DIFFUSE OPTICAL IMAGING OF VULNERABLE TISSUE HEMODYNAMICS

Measurement of tissue hemodynamics provides vital information for the assessment of tissue viability. This thesis reports three noninvasive near-infrared diffuse optical systems for spectroscopic measurements and tomographic imaging of tissue hemodynamics in vulnerable tissues with the goal of disease diagnosis and treatment monitoring. A hybrid near-infrared spectroscopy/diffuse correlation spectroscopy (NIRS/DCS) instrument with a contact fiber-optic probe was developed and utilized for simultaneous and continuous monitoring of blood flow (BF), blood oxygenation, and oxidative metabolism in exercising gastrocnemius. Results measured by the hybrid NIRS/DCS instrument in 37 subjects (mean age: 67 ± 6) indicated that vitamin D supplement plus aerobic training improved muscle metabolic function in older population. To reduce the interference and potential infection risk on vulnerable tissues caused by the contact measurement, a noncontact diffuse correlation spectroscopy/tomography (ncDCS/ncDCT) system was then developed. The ncDCS/ncDCT system employed optical lenses to project limited numbers of sources and detectors on the tissue surface. A motor-driven noncontact probe scanned over a region of interest to collect boundary data for three dimensional (3D) tomographic imaging of blood flow distribution. The ncDCS was tested for BF measurements in mastectomy skin flaps. Nineteen (19) patients underwent mastectomy and implant-based breast reconstruction were measured before and immediately after mastectomy. The BF index after mastectomy in each patient was normalized to its baseline value before surgery to get relative BF (rBF). Since rBF values in the patients with necrosis (n = 4) were significantly lower than those without necrosis (n = 15), rBF levels can be used to predict mastectomy skin flap necrosis. The ncDCT was tested for 3D imaging of BF distributions in chronic wounds of 5 patients. Spatial variations in BF contrasts over the wounded tissues were observed, indicating the capability of ncDCT in detecting tissue hemodynamic heterogeneities. To improve temporal/spatial resolution and avoid motion artifacts due to a long mechanical scanning of ncDCT, an electron-multiplying charge-coupled device based noncontact speckle contrast diffuse correlation tomography (scDCT) was developed. Validation of scDCT was done by imaging both high and low BF contrasts in tissue-like phantoms and human forearms. In a wound imaging study using scDCT, significant lower BF values were observed in the burned areas/volumes compared to surrounding normal tissues in two patients with burn. One limitation in this study was the potential influence of other unknown tissue optical properties such as tissue absorption coefficient (µa) on BF measurements. A new algorithm was then developed to extract both µa and BF using light intensities and speckle contrasts measured by scDCT at multiple source-detector distances. The new algorithm was validated using tissue-like liquid phantoms with varied values of µa and BF index. In-vivo validation and application of the innovative scDCT technique with the new algorithm is the subject of future work