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

BACKGROUND: 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. METHODS: IH was quantified by continuously monitoring oxygen saturation (SpO2) using high-resolution pulse oximeters during the first 10 weeks of life. Statistical analyses assessed the relationship and predictive ability of weekly and cumulative IH for Type 1 ROP development. RESULTS: Most analyses showed no association between IH and Type 1 ROP adjusting for gestational age (GA) and birth weight (BW). However, cumulative IH of longer duration during weeks 5-10, 6-10, and 7-10 were significantly associated with Type 1 ROP adjusting for GA and BW, e.g., the adjusted odds ratio of Type 1 ROP was 2.01 (p = 0.03) for every 3.8 seconds increase in IH duration from week 6-10. IH did not provide statistically significant added predictive ability above GA and BW. CONCLUSIONS: For most analyses there was no significant association between IH and Type 1 ROP adjusting for GA and BW. However, infants with longer IH duration during the second month of life had higher risk for Type 1 ROP. IMPACT: The relationship and predictive ability of intermittent hypoxemia (IH) on retinopathy of prematurity (ROP) is controversial. This study shows no significant association between IH events and Type 1 ROP after adjusting for gestational age (GA) and birth weight (BW), except for cumulative IH of longer duration in the second month of life. In this cohort, IH does not provide a statistically significant improvement in ROP prediction over GA and BW. This study is the first to assess the cumulative impact of IH measures on Type 1 ROP. Interventions for reducing IH duration during critical postnatal periods may improve ROP outcomes.

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

BACKGROUND: 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. METHODS: DSCFO uses two small laser diodes as focused-point and a tiny CMOS camera as a high-density two-dimensional detector to detect spontaneous spatial fluctuation of diffuse laser speckles for CBF measurement, and light intensity attenuations for cerebral oxygenation measurement. The DSCFO was first validated against the established diffuse correlation spectroscopy (DCS) in neonatal piglets and then utilized for continuous CBF and oxygenation monitoring in preterm infants during intermittent hypoxemia (IH) events. RESULTS: Significant correlations between the DSCFO and DCS measurements of CBF variations in neonatal piglets were observed. IH events induced fluctuations in CBF, cerebral oxygenation, and peripheral cardiorespiratory vitals in preterm infants. However, no consistent correlation patterns were observed among peripheral and cerebral monitoring parameters. CONCLUSIONS: This pilot study demonstrated the feasibility of DSCFO technology to serve as a low-cost wearable sensor for continuous monitoring of multiple cerebral hemodynamic parameters. The results suggested the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations. IMPACT: The innovative DSCFO technology may serve as a low-cost wearable sensor for continuous bedside monitoring of multiple cerebral hemodynamic parameters in neonatal intensive care units. Concurrent DSCFO and DCS measurements of CBF variations in neonatal piglet models generated consistent results. No consistent correlation patterns were observed among peripheral and cerebral monitoring parameters in preterm neonates, suggesting the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations during IH events. Integrating and correlating multiple cerebral functional parameters with clinical outcomes may identify biomarkers for prediction and management of IH associated brain injury.

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

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.

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

Significance: 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. Aim: We investigate a new diffuse speckle contrast topography (DSCT) method with parallel computation for analyzing scDCT data to achieve fast and high-density two-dimensional (2D) mapping of CBF distributions at different depths without the need for 3D reconstruction. Approach: A new moving window method was adapted to improve the sampling rate of DSCT. A fast computation method utilizing MATLAB functions in the Image Processing Toolbox™ and Parallel Computing Toolbox™ was developed to rapidly generate high-density CBF maps. The new DSCT method was tested for spatial resolution and depth sensitivity in head-simulating layered phantoms and in-vivo rodent models. Results: DSCT enables 2D mapping of the particle flow in the phantom at different depths through the top layer with varied thicknesses. Both DSCT and scDCT enable the detection of global and regional CBF changes in deep brains of adult rats. However, DSCT achieves fast and high-density 2D mapping of CBF distributions at different depths without the need for complex and time-consuming 3D reconstruction. Conclusions: The depth-sensitive DSCT method has the potential to be used as a noninvasive, noncontact, fast, high resolution, portable, and inexpensive brain imager for basic neuroscience research in small animal models and for translational studies in human neonates.

A Wearable Fiber-Free Optical Sensor for Continuous Monitoring of Neonatal Cerebral Blood Flow and Oxygenation.

Impact: The innovative DSCFO technology may serve as a low-cost wearable sensor for continuous bedside monitoring of multiple cerebral hemodynamic parameters in neonatal intensive care units.Concurrent DSCFO and DCS measurements of CBF variations in neonatal piglet models generated consistent results.No consistent correlation patterns were observed among peripheral and cerebral monitoring parameters in preterm neonates, suggesting the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations during IH events.Integrating and correlating multiple cerebral functional parameters with clinical outcomes may identify biomarkers for prediction and management of IH associated brain injury. Background: 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. Methods: DSCFO uses two small laser diodes as focused-point and a tiny CMOS camera as a high-density two-dimensional detector to detect spontaneous spatial fluctuation of diffuse laser speckles for CBF measurement, and light intensity attenuations for cerebral oxygenation measurement. The DSCFO was first validated against the established diffuse correlation spectroscopy (DCS) in neonatal piglets and then utilized for continuous CBF and oxygenation monitoring in preterm infants during intermittent hypoxemia (IH) events. Results: Consistent results between the DSCFO and DCS measurements of CBF variations in neonatal piglets were observed. IH events induced fluctuations in CBF, cerebral oxygenation, and peripheral cardiorespiratory vitals in preterm infants. However, no consistent correlation patterns were observed among peripheral and cerebral monitoring parameters. Conclusions: This pilot study demonstrated the feasibility of DSCFO technology to serve as a low-cost wearable sensor for continuous monitoring of multiple cerebral hemodynamic parameters. The results suggested the importance of multi-parameter measurements for understanding deep insights of peripheral and cerebral regulations.

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

Background: 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. Methods: IH was quantified by continuously monitoring oxygen saturation (SpO2) using high-resolution pulse oximeters during the first 10 weeks of life. Statistical analyses assessed the relationship and predictive ability of weekly and cumulative IH variables for Type 1 ROP development. Results: Univariate analyses suggested that IH measures are greater in infants with Type 1 ROP and are predictive of Type 1 ROP development. Multivariable logistic regression analyses revealed that cumulative IH of longer duration during certain postnatal periods are associated with Type 1 ROP development after adjusting for gestational age (GA) or birth weight (BW). Although area under the curve (AUC) analyses revealed added predictivity of cumulative IH variables above GA or BW, these increments in AUC were not statistically significant. Conclusions: The duration of IH events was associated with Type 1 ROP development. Interventions for reducing the duration of IH events may potentially improve ROP outcomes.

Intraoperative Optical and Fluorescence Imaging of Blood Flow Distributions in Mastectomy Skin Flaps for Identifying Ischemic Tissues.

SUMMARY: Insufficient blood flow causes mastectomy skin flap necrosis in 5 to 30 percent of cases. Fluorescence angiography with the injection of indocyanine green dye has shown high sensitivities (90 to 100 percent) but moderate specificities (72 to 50 percent) in predicting mastectomy skin flap necrosis. However, a number of challenging issues limit its wide acceptance in clinical settings, including allergic reaction, short time-window for observation, and high cost for equipment and supplies. An emerging inexpensive speckle contrast diffuse correlation tomography technology enables noninvasive, noncontact, and continuous three-dimensional imaging of blood flow distributions in deep tissues. This preliminary study tested the hypothesis that speckle contrast diffuse correlation tomography and indocyanine green-fluorescence angiography measurements of blood flow distributions in mastectomy skin flaps are consistent. Eleven female patients undergoing skin-sparing or nipple-sparing mastectomies were imaged sequentially by the dye-free speckle contrast diffuse correlation tomography and dye-based commercial fluorescence angiography (SPY-PHI). Resulting images from these two imaging modalities were co-registered based on the ischemic areas with the lowest blood flow values. Because the ischemic areas have irregular shapes, a novel contour-based algorithm was used to compare three-dimensional images of blood flow distribution and two-dimensional maps of indocyanine green perfusion. Significant correlations were observed between the two measurements in all contours from a selected area of 10 × 10 mm 2 with the lowest blood flow ( r ≥ 0.78; p < 0.004), suggesting that speckle contrast diffuse correlation tomography provides the information for identifying ischemic tissues in mastectomy skin flaps. With further optimization and validation in large populations, speckle contrast diffuse correlation tomography may ultimately be used as a noninvasive and inexpensive imaging tool for intraoperative assessment of skin flap viability to predict mastectomy skin flap necrosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

Speckle contrast diffuse correlation tomography of cerebral blood flow in perinatal disease model of neonatal piglets.

We adapted and tested an innovative noncontact speckle contrast diffuse correlation tomography (scDCT) system for 3D imaging of cerebral blood flow (CBF) variations in perinatal disease models utilizing neonatal piglets, which closely resemble human neonates. CBF variations were concurrently measured by the scDCT and an established diffuse correlation spectroscopy (DCS) during global ischemia, intraventricular hemorrhage, and asphyxia; significant correlations were observed. Moreover, CBF variations associated reasonably with vital pathophysiological changes. In contrast to DCS measurements of mixed signals from local scalp, skull and brain, scDCT generates 3D images of CBF distributions at prescribed depths within the head, thus enabling specific determination of regional cerebral ischemia. With further optimization and validation in animals and human neonates, scDCT has the potential to be a noninvasive imaging tool for both basic neuroscience research in laboratories and clinical applications in neonatal intensive care units.

A Neonatal Bimodal MR-CT Head Template.

Neonatal MR templates are appropriate for brain structural analysis and spatial normalization. However, they do not provide the essential accurate details of cranial bones and fontanels-sutures. Distinctly, CT images provide the best contrast for bone definition and fontanels-sutures. In this paper, we present, for the first time, an approach to create a fully registered bimodal MR-CT head template for neonates with a gestational age of 39 to 42 weeks. Such a template is essential for structural and functional brain studies, which require precise geometry of the head including cranial bones and fontanels-sutures. Due to the special characteristics of the problem (which requires inter-subject inter-modality registration), a two-step intensity-based registration method is proposed to globally and locally align CT images with an available MR template. By applying groupwise registration, the new neonatal CT template is then created in full alignment with the MR template to build a bimodal MR-CT template. The mutual information value between the CT and the MR template is 1.17 which shows their perfect correspondence in the bimodal template. Moreover, the average mutual information value between normalized images and the CT template proposed in this study is 1.24±0.07. Comparing this value with the one reported in a previously published approach (0.63±0.07) demonstrates the better generalization properties of the new created template and the superiority of the proposed method for the creation of CT template in the standard space provided by MR neonatal head template. The neonatal bimodal MR-CT head template is freely downloadable from https://www.u-picardie.fr/labo/GRAMFC.