fabrication-an-expandable-brain-matrix-customizable-across

Fabrication of an Expandable Brain Matrix Customizable Across Developmental Stages

Increasing interest in using newborn piglets as a study model for neonatal development and pathology has raised the need for a brain matrix to accurately ...

University of Kentucky

There is an essential need to develop wearable multimodality technologies that can continuously measure both blood flow and oxygenation in deep tissues to investigate and manage various vascular/cellular diseases.

Simultaneous measurements of tissue blood flow and oxygenation using a wearable fiber-free optical sensor.

Intermittent hypoxemia (IH) may influence retinopathy of prematurity (ROP) development in preterm infants, however, previous studies had mixed results. This study aims to assess the influence and evaluate the predictive ability of IH measures on Type 1 ROP, a stage beyond which ROP treatment is indicated.

The Impact of Intermittent Hypoxemia on Type 1 Retinopathy of Prematurity in Preterm Infants.

Frequent assessment of cerebral blood flow (CBF) is crucial for the diagnosis and management of cerebral vascular diseases. In contrast to large and expensive imaging modalities, such as nuclear medicine and magnetic resonance imaging, optical imaging techniques are portable and inexpensive tools for continuous measurements of cerebral hemodynamics. The recent development of an innovative noncontact speckle contrast diffuse correlation tomography (scDCT) enables three-dimensional (3D) imaging of CBF distributions. However, scDCT requires complex and time-consuming 3D reconstruction, which limits its ability to achieve high spatial resolution without sacrificing temporal resolution and computational efficiency.

Depth-sensitive diffuse speckle contrast topography for high-density mapping of cerebral blood flow in rodents.

Malignant glioma (MG) is the most common type of primary malignant brain tumors. Surgical resection of MG remains the cornerstone of therapy and the extent of resection correlates with patient survival. A limiting factor for resection, however, is the difficulty in differentiating the tumor from normal tissue during surgery. Fluorescence imaging is an emerging technique for real-time intraoperative visualization of MGs and their boundaries. However, most clinical grade neurosurgical operative microscopes with fluorescence imaging ability are hampered by low adoption rates due to high cost, limited portability, limited operation flexibility, and lack of skilled professionals with technical knowledge. To overcome the limitations, we innovatively integrated miniaturized light sources, flippable filters, and a recording camera to the surgical eye loupes to generate a wearable fluorescence eye loupe (FLoupe) device for intraoperative imaging of fluorescent MGs. Two FLoupe prototypes were constructed for imaging of Fluorescein and 5-aminolevulinic acid (5-ALA), respectively. The wearable FLoupe devices were tested on tumor-simulating phantoms and patients with MGs. Comparable results were observed against the standard neurosurgical operative microscope (PENTERO® 900) with fluorescence kits. The affordable and wearable FLoupe devices enable visualization of both color and fluorescence images with the same quality as the large and expensive stationary operative microscopes. The wearable FLoupe device allows for a greater range of movement, less obstruction, and faster/easier operation. Thus, it reduces surgery time and is more easily adapted to the surgical environment than unwieldy neurosurgical operative microscopes. Clinical and Translational Impact Statement-The affordable and wearable fluorescence imaging device developed in this study enables neurosurgeons to observe brain tumors with the same clarity and greater flexibility compared to bulky and costly operative microscopes.

A Wearable Fluorescence Imaging Device for Intraoperative Identification of Human Brain Tumors.

Unstable cerebral hemodynamics places preterm infants at high risk of brain injury. We adapted an innovative, fiber-free, wearable diffuse speckle contrast flow-oximetry (DSCFO) device for continuous monitoring of both cerebral blood flow (CBF) and oxygenation in neonatal piglets and preterm infants.

Wearable fiber-free optical sensor for continuous monitoring of neonatal cerebral blood flow and oxygenation.

Intermittent hypoxemia (IH) may influence retinopathy of prematurity (ROP) development in preterm infants, however, previous studies had mixed results. This study tests the hypothesis that increased IH is associated with Type 1 ROP; a stage beyond which treatment is indicated.

The impact of intermittent hypoxemia on type 1 retinopathy of prematurity in preterm infants.

Cerebral blood flow (CBF) imaging is crucial for diagnosing cerebrovascular diseases. However, existing large neuroimaging techniques with high cost, low sampling rate, and poor mobility make them unsuitable for continuous and longitudinal CBF monitoring at the bedside.

Programmable scanning diffuse speckle contrast imaging of cerebral blood flow.

Measuring cerebral blood flow (CBF) is crucial for diagnosing various cerebral diseases. An affordable, wearable, and fiber-free continuous-wave speckle contrast flowmetry (CW-DSCF) technique has been developed for continuous monitoring of CBF variations. However, its application in adult humans is limited by shallow tissue penetration.

An affordable, wearable, fiber-free pulsed-mode diffuse speckle contrast flowmetry (PM-DSCF) sensor for noninvasive measurements of deep cerebral blood flow.

Low-frequency oscillations (LFOs) (  ) with respect to cerebral blood flow (CBF) have shown promise as an indicator of altered neurologic activity in the abnormal brain. Portable optical instruments have evolved to offer a noninvasive alternative for continuous CBF monitoring at the bedside compared with many large neuroimaging modalities. However, their utilization for acquiring LFOs of CBF has only been studied to a limited extent.

Detection of low-frequency oscillations in neonatal piglets with speckle contrast diffuse correlation tomography.

Perioperative identification of ischemic-hypoxic tissue is essential for reducing the risk of mastectomy skin flap necrosis (MSFN), a major complication following mastectomy. Implant-based breast reconstruction is jeopardized in the presence of MSFN. However, existing technologies are limited by depth insensitivity, dye-related risks, the need for contact sensors, and an inability to simultaneously assess both blood flow and oxygenation. A multi-wavelength speckle contrast diffuse correlation tomography (MW-scDCT) system was developed for noncontact, dye-free, and depth-sensitive imaging of tissue hemodynamics in a rat model incorporating four distinct flap scenarios: sham (SH), implant (IM), half necrosis (HN), and full necrosis (FN), representing varying degrees of tissue viability. MW-scDCT measured longitudinal changes in relative blood flow index (  ) and oxy- and deoxy-hemoglobin concentrations (  and  ) over seven days. Repeated measures analysis of variance and quadratic discriminant analysis were employed for statistical analysis. MW-scDCT enabled longitudinal imaging of tissue blood flow and oxygenation distributions, revealing significant differences across flap types and over time. In terms of discriminative power, integrating  ,  , and  into a multivariable classification model substantially improved accuracy, achieving 80-95% compared to 40-70% using individual parameters. Binary classification of necrotic (FN + HN) versus non-necrotic (SH + IM) flaps showed up to 50% improvement in accuracy gains. MW-scDCT effectively distinguished necrotic from viable flaps and provided critical early postoperative insights into MSFN. These findings support its potential clinical utility as a perioperative monitoring tool to guide decision-making, reduce flap failure risk, and improve reconstructive outcomes.

Article	Year
Simultaneous measurements of tissue blood flow and oxygenation using a wearable fiber-free optical sensor. Journal of biomedical optics\| PubMed ID: 33515216	2021
The Impact of Intermittent Hypoxemia on Type 1 Retinopathy of Prematurity in Preterm Infants. medRxiv : the preprint server for health sciences\| PubMed ID: 37808800	2023
Depth-sensitive diffuse speckle contrast topography for high-density mapping of cerebral blood flow in rodents. Neurophotonics\| PubMed ID: 38076725	2023
A Wearable Fluorescence Imaging Device for Intraoperative Identification of Human Brain Tumors. IEEE journal of translational engineering in health and medicine\| PubMed ID: 38196823	2024
Wearable fiber-free optical sensor for continuous monitoring of neonatal cerebral blood flow and oxygenation. Pediatric research\| PubMed ID: 38503982	2024
The impact of intermittent hypoxemia on type 1 retinopathy of prematurity in preterm infants. Pediatric research\| PubMed ID: 38600299	2024
Programmable scanning diffuse speckle contrast imaging of cerebral blood flow. ArXiv\| PubMed ID: 39253639	2024
Programmable scanning diffuse speckle contrast imaging of cerebral blood flow. Neurophotonics\| PubMed ID: 39872020	2025
An affordable, wearable, fiber-free pulsed-mode diffuse speckle contrast flowmetry (PM-DSCF) sensor for noninvasive measurements of deep cerebral blood flow. ArXiv\| PubMed ID: 39990801	2025
Detection of low-frequency oscillations in neonatal piglets with speckle contrast diffuse correlation tomography. Journal of biomedical optics\| PubMed ID: 40060305	2023
Noncontact diffuse optical imaging of blood flow and oxygenation distributions in reconstructive rat skin flaps. Biomedical optics express\| PubMed ID: 41368087	2025

Xuhui Liu

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