Faculty Bibliography

BACKGROUND:The association between sleep and Alzheimer's disease (AD) biomarkers are well-established, but little is known about how they interact to change the course of AD. OBJECTIVE:To determine the potential interaction between sleep disturbance and Aβ, tau, and APOE4 on brain atrophy and cognitive decline. METHODS:Sample included 351 participants (mean age 72.01 ± 6.67, 50.4%female) who were followed for approximately 5 years as part of the Alzheimer's Disease Neuroimaging Initiative. Informant-reported sleep disturbance (IRSD) was measured using the Neuropsychiatric Inventory (NPI). Changes in magnetic resonance imaging (MRI)-measured AD signature brain regions and cognitive performance and IRSD's interaction with cerebrospinal fluid amyloid-β (Aβ42) and p-Tau depositions and APOE4 status were examined using the linear mixed models. RESULTS:Baseline IRSD was not significantly associated with the rate of atrophy after adjusting for covariates (age, sex, education, total NPI severity score, and sleep medications). However, there was a significant interaction between IRSD and AD biomarkers on faster atrophy rates in multiple brain regions, including the cortical and middle temporal volumes. Post-hoc analyses indicated that Aβ and p-Tau/Aβ predicted a faster decline in these regions/domains in IRSD, compared with biomarker-negative individuals with IRSD (ps≤0.001). There was a significant IRSD*APOE4 interaction for brain atrophy rate (ps≤0.02) but not for cognition. CONCLUSION:IRSD may increase the future risk of AD by contributing to faster brain atrophy and cognitive decline when combined with the presence of AD biomarkers and APOE4. Early intervention for sleep disturbance could help reduce the risk of developing AD.

We introduce a novel image reconstruction method for time-resolved diffuse optical tomography (DOT) that yields submillimeter resolution in less than a second. This opens the door to high-resolution real-time DOT in imaging of the brain activity. We call this approach the sensitivity equation based noniterative sparse optical reconstruction (SENSOR) method. The high spatial resolution is achieved by implementing an asymptotic l ₀-norm operator that guarantees to obtain sparsest representation of reconstructed targets. The high computational speed is achieved by employing the nontruncated sensitivity equation based noniterative inverse formulation combined with reduced sensing matrix and parallel computing. We tested the new method with numerical and experimental data. The results demonstrate that the SENSOR algorithm can achieve 1 mm³ spatial-resolution optical tomographic imaging at depth of ∼60 mean free paths (MFPs) in 20∼30 milliseconds on an Intel Core i9 processor.

PURPOSE/OBJECTIVE:Diffuse optical tomography breast imaging system (DOTBIS) non-invasively measures tissue concentration of hemoglobin, which is a potential biomarker of short-term response to neoadjuvant chemotherapy. We evaluated whether DOTBIS-derived measurements are modifiable with targeted therapies, including AKT inhibition and endocrine therapy. METHODS:Hb), and deoxyhemoglobin (ctHHb), as well as water fraction (%). RESULTS:Hb, and water fraction were + 1.8% (IQR 26.7%), - 8.6% (IQR 29.3%), + 6.2% (IQR 29.5%), and + 1.9% (IQR 30.7%), respectively. CONCLUSION/CONCLUSIONS:We demonstrated that DOTBIS-derived measurements are modifiable with pre-surgical AKT inhibition and endocrine therapy, supporting further investigation of DOTBIS as a potential imaging assessment of response to neoadjuvant targeted therapies in early stage breast cancer.

Light scattering by tissue severely limits how deep beneath the surface one can image, and the spatial resolution one can obtain from these images. Diffuse optical tomography (DOT) is one of the most powerful techniques for imaging deep within tissue - well beyond the conventional  ∼ 10-15 mean scattering lengths tolerated by ballistic imaging techniques such as confocal and two-photon microscopy. Unfortunately, existing DOT systems are limited, achieving only centimeter-scale resolution. Furthermore, they suffer from slow acquisition times and slow reconstruction speeds making real-time imaging infeasible. We show that time-of-flight diffuse optical tomography (ToF-DOT) and its confocal variant (CToF-DOT), by exploiting the photon travel time information, allow us to achieve millimeter spatial resolution in the highly scattered diffusion regime ( mean free paths). In addition, we demonstrate two additional innovations: focusing on confocal measurements, and multiplexing the illumination sources allow us to significantly reduce the measurement acquisition time. Finally, we rely on a novel convolutional approximation that allows us to develop a fast reconstruction algorithm, achieving a 100× speedup in reconstruction time compared to traditional DOT reconstruction techniques. Together, we believe that these technical advances serve as the first step towards real-time, millimeter resolution, deep tissue imaging using DOT.

PURPOSE:This study's primary objective was to evaluate the changes in optically derived parameters acquired with a diffuse optical tomography breast imaging system (DOTBIS) in the tumor volume of patients with breast carcinoma receiving neoadjuvant chemotherapy (NAC). EXPERIMENTAL DESIGN:In this analysis of 105 patients with stage II-III breast cancer, normalized mean values of total hemoglobin ([Formula: see text]), oxyhemoglobin ([Formula: see text]), deoxy-hemoglobin concentration ([Formula: see text]), water, and oxygen saturation ([Formula: see text]) percentages were collected at different timepoints during NAC and compared with baseline measurements. This report compared changes in these optical biomarkers measured in patients who did not achieve a pathologic complete response (non-pCR) and those with a pCR. Differences regarding molecular subtypes were included for hormone receptor-positive and HER2-negative, HER2-positive, and triple-negative breast cancer. RESULTS:< 0.0005; and 95% confidence interval, 0.812-0.969. CONCLUSIONS:This study demonstrates that DOTBIS measured features change over time according to tumor pCR status and may predict early in the NAC treatment course whether a patient is responding to NAC.

We have developed a flexible optical imaging system (FOIS) to assess systemic lupus erythematosus (SLE) arthritis in the finger joints. While any part of the body can be affected, arthritis in the finger joints is one of the most common SLE manifestations. There is an unmet need for accurate, low-cost assessment of lupus arthritis that can be easily performed at every clinic visit. Current imaging methods are imprecise, expensive, and time consuming to allow for frequent monitoring. Our FOIS can be wrapped around joints, and multiple light sources and detectors gather reflected and transmitted light intensities. Using data from two SLE patients and two healthy volunteers, we demonstrate the potential of this FOIS for assessment of arthritis in SLE patients.

BACKGROUND:The purpose of this study is to evaluate whether the changes in optically derived parameters acquired with a diffuse optical tomography breast imager system (DOTBIS) in the contralateral non-tumor-bearing breast in patients administered neoadjuvant chemotherapy (NAC) for breast cancer are associated with pathologic complete response (pCR). METHODS:Hb changes across chemotherapy when corrected for pCR status, age, and BMI. RESULTS:Hb levels with BMI and age. CONCLUSIONS:This study demonstrates that the contralateral normal breast tissue assessed by DOTBIS is modifiable after NAC, with changes associated with pCR after only 2-3 weeks of chemotherapy.