Clinical Validation of a Prenatal Cell-Free DNA Screening Test for Fetal RHD in a Large U.S. Cohort.

Objective: To present a large U.S. clinical validation of a next-generation sequencing-based, noninvasive prenatal cell-free DNA test for fetal RHD.

ninjaNIRS: an open hardware solution for wearable whole-head high-density functional near-infrared spectroscopy.

Functional near-infrared spectroscopy (fNIRS) technology has been steadily advancing since the first measurements of human brain activity over 30 years ago. Initially, efforts were focused on increasing the channel count of fNIRS systems and then to moving from sparse to high density arrays of sources and detectors, enhancing spatial resolution through overlapping measurements. Over the last ten years, there have been rapid developments in wearable fNIRS systems that place the light sources and detectors on the head as opposed to the original approach of using fiber optics to deliver the light between the hardware and the head.

ninjaCap: a fully customizable and 3D printable headgear for functional near-infrared spectroscopy and electroencephalography brain imaging.

Accurate sensor placement is vital for non-invasive brain imaging, particularly for functional near-infrared spectroscopy (fNIRS) and diffuse optical tomography (DOT), which lack standardized layouts such as those in electroencephalography (EEG). Custom, manually prepared probe layouts on textile caps are often imprecise and labor intensive. We introduce a method for creating personalized, 3D-printed headgear, enabling the accurate translation of 3D brain coordinates to 2D printable panels for custom fNIRS and EEG sensor layouts while reducing costs and manual labor.

ninjaCap: A fully customizable and 3D printable headgear for fNIRS and EEG brain imaging.

Significance: Accurate sensor placement is vital for non-invasive brain imaging, particularly for functional near infrared spectroscopy (fNIRS) and diffuse optical tomography (DOT), which lack standardized layouts like EEG. Custom, manually prepared probe layouts on textile caps are often imprecise and labor-intensive.

Aim: We introduce a method for creating personalized, 3D-printed headgear, enabling accurate translation of 3D brain coordinates to 2D printable panels for custom fNIRS and EEG sensor layouts, reducing costs and manual labor.

Choosing a camera and optimizing system parameters for speckle contrast optical spectroscopy.

Speckle contrast optical spectroscopy (SCOS) is an emerging camera-based technique that can measure human cerebral blood flow (CBF) with high signal-to-noise ratio (SNR). At low photon flux levels typically encountered in human CBF measurements, camera noise and nonidealities could significantly impact SCOS measurement SNR and accuracy. Thus, a guide for characterizing, selecting, and optimizing a camera for SCOS measurements is crucial for the development of next-generation optical devices for monitoring human CBF and brain function.

Serial Postoperative Circulating Tumor DNA Assessment Has Strong Prognostic Value During Long-Term Follow-Up in Patients With Breast Cancer.

Purpose: Here, we report the sensitivity of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay (Signatera) for detection of molecular relapse during long-term follow-up of patients with breast cancer.

Methods: A total of 156 patients with primary breast cancer were monitored clinically for up to 12 years after surgery and adjuvant chemotherapy. Semiannual blood samples were prospectively collected, and analyzed retrospectively to detect residual disease by ultradeep sequencing using ctDNA assays, developed from primary tumor whole-exome sequencing data.

Multi-wavelength multi-distance diffuse correlation spectroscopy system for assessment of premature infants' cerebral hemodynamics.

Infants born at an extremely low gestational age (ELGA, < 29 weeks) are at an increased risk of intraventricular hemorrhage (IVH), and there is a need for standalone, safe, easy-to-use tools for monitoring cerebral hemodynamics. We have built a multi-wavelength multi-distance diffuse correlation spectroscopy device (MW-MD-DCS), which utilizes time-multiplexed, long-coherence lasers at 785, 808, and 853 nm, to simultaneously quantify the index of cerebral blood flow (CBF) and the hemoglobin oxygen saturation (SO). We show characterization data on liquid phantoms and demonstrate the system performance on the forearm of healthy adults, as well as clinical data obtained on two preterm infants.

Correlation between variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors.

Several studies have demonstrated the prognostic value of circulating tumor DNA (ctDNA); however, the correlation of mean tumor molecules (MTM)/ml of plasma and mean variant allele frequency (mVAF; %) with clinical parameters is yet to be understood. In this study, we analyzed ctDNA data in a pan-cancer cohort of 23 543 patients who had ctDNA testing performed using a personalized, tumor-informed assay (Signatera™, mPCR-NGS assay). For ctDNA-positive patients, the correlation between MTM/ml and mVAF was examined.

Measuring human cerebral blood flow and brain function with fiber-based speckle contrast optical spectroscopy system.

Cerebral blood flow (CBF) is crucial for brain health. Speckle contrast optical spectroscopy (SCOS) is a technique that has been recently developed to measure CBF, but the use of SCOS to measure human brain function at large source-detector separations with comparable or greater sensitivity to cerebral rather than extracerebral blood flow has not been demonstrated. We describe a fiber-based SCOS system capable of measuring human brain activation induced CBF changes at 33 mm source detector separations using CMOS detectors.

Model of dynamic speckle evolution for evaluating laser speckle contrast measurements of tissue dynamics.

We introduce a dynamic speckle model (DSM) to simulate the temporal evolution of fully developed speckle patterns arising from the interference of scattered light reemitted from dynamic tissue. Using this numerical tool, the performance of laser speckle contrast imaging (LSCI) or speckle contrast optical spectroscopy (SCOS) systems which quantify tissue dynamics using the spatial contrast of the speckle patterns with a certain camera exposure time is evaluated. We have investigated noise sources arising from the fundamental speckle statistics due to the finite sampling of the speckle patterns as well as those induced by experimental measurement conditions including shot noise, camera dark and read noise, and calibrated the parameters of an analytical noise model initially developed in the fundamental or shot noise regime that quantifies the performance of SCOS systems using the number of independent observables (NIO).

How much do time-domain functional near-infrared spectroscopy (fNIRS) moments improve estimation of brain activity over traditional fNIRS?

Significance: Advances in electronics have allowed the recent development of compact, high channel count time domain functional near-infrared spectroscopy (TD-fNIRS) systems. Temporal moment analysis has been proposed for increased brain sensitivity due to the depth selectivity of higher order temporal moments. We propose a general linear model (GLM) incorporating TD moment data and auxiliary physiological measurements, such as short separation channels, to improve the recovery of the HRF.

Circulating tumor DNA monitoring for early recurrence detection in epithelial ovarian cancer.

Objective: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. We examined the utility of circulating tumor DNA (ctDNA) as a prognostic biomarker for EOC by assessing its relationship with patient outcome and CA-125, pre-surgically and during post-treatment surveillance.

Methods: Plasma samples were collected from patients with stage I-IV EOC.

Clinical Validation of a Plasma Donor-derived Cell-free DNA Assay to Detect Allograft Rejection and Injury in Lung Transplant.

Background: Lung transplant patients are vulnerable to various forms of allograft injury, whether from acute rejection (AR) (encompassing acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), chronic lung allograft dysfunction (CLAD), or infection (INFXN). Previous research indicates that donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive biomarker for the detection of AR and allograft injury. Our aim was to validate a clinical plasma dd-cfDNA assay for detection of AR and other allograft injury and to confirm and expand on dd-cfDNA and allograft injury associations observed in previous studies.

Donor-derived Cell-free DNA Shows High Sensitivity for the Diagnosis of Pancreas Graft Rejection in Simultaneous Pancreas-kidney Transplantation.

Background: Pancreas graft status in simultaneous pancreas-kidney transplant (SPKTx) is currently assessed by nonspecific biochemical markers, typically amylase or lipase. Identifying a noninvasive biomarker with good sensitivity in detecting early pancreas graft rejection could improve SPKTx management.

Methods: Here, we developed a pilot study to explore donor-derived cell-free DNA (dd-cfDNA) performance in predicting biopsy-proven acute rejection (P-BPAR) of the pancreas graft in a cohort of 36 SPKTx recipients with biopsy-matched plasma samples.

Assessment of Molecular Residual Disease Using Circulating Tumor DNA to Identify Multiple Myeloma Patients at High Risk of Relapse.

Background: Despite treatment with high-dose chemotherapy followed by autologous stem cell transplantation (AHCT), patients with multiple myeloma (MM) invariably relapse. Molecular residual disease (MRD)-negativity post-AHCT has emerged as an important prognostic marker predicting the duration of remission. Current techniques for MRD assessment involve bone marrow (BM) aspirate sampling, which is invasive, subject to sample variability and is limited by spatial heterogeneity.

Detection of Molecular Residual Disease Using Personalized Circulating Tumor DNA Assay in Patients With Colorectal Cancer Undergoing Resection of Metastases.

Purpose: More than 50% of patients with stage IV colorectal cancer (metastatic colorectal cancer [mCRC]) relapse postresection. The efficacy of postoperative systemic treatment is limited in this setting. Thus, these patients would greatly benefit from the use of a reliable prognostic biomarker, such as circulating tumor DNA (ctDNA) to identify minimal or molecular residual disease (MRD).

ctDNA guiding adjuvant immunotherapy in urothelial carcinoma.

Minimally invasive approaches to detect residual disease after surgery are needed to identify patients with cancer who are at risk for metastatic relapse. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease and relapse. We evaluated outcomes in 581 patients who had undergone surgery and were evaluable for ctDNA from a randomized phase III trial of adjuvant atezolizumab versus observation in operable urothelial cancer.

Circulating tumor DNA and magnetic resonance imaging to predict neoadjuvant chemotherapy response and recurrence risk.

We investigated whether serial measurements of circulating tumor DNA (ctDNA) and functional tumor volume (FTV) by magnetic resonance imaging (MRI) can be combined to improve prediction of pathologic complete response (pCR) and estimation of recurrence risk in early breast cancer patients treated with neoadjuvant chemotherapy (NAC). We examined correlations between ctDNA and FTV, evaluated the additive value of ctDNA to FTV-based predictors of pCR using area under the curve (AUC) analysis, and analyzed the impact of FTV and ctDNA on distant recurrence-free survival (DRFS) using Cox regressions. The levels of ctDNA (mean tumor molecules/mL plasma) were significantly correlated with FTV at all time points (p < 0.

Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab.

Immune checkpoint blockade (ICB) provides clinical benefit to a subset of patients with cancer. However, existing biomarkers do not reliably predict treatment response across diverse cancer types. Limited data exist to show how serial circulating tumor DNA (ctDNA) testing may perform as a predictive biomarker in patients receiving ICB.

The effect of surgical trauma on circulating free DNA levels in cancer patients-implications for studies of circulating tumor DNA.

Detection of circulating tumor DNA (ctDNA) post-treatment is an emerging marker of residual disease. ctDNA constitutes only a minor fraction of the cell-free DNA (cfDNA) circulating in cancer patients, complicating ctDNA detection. This is exacerbated by trauma-induced cfDNA.

Contribution of speckle noise in near-infrared spectroscopy measurements.

Near-infrared spectroscopy (NIRS) is widely used in biomedical optics with applications ranging from basic science, such as in functional neuroimaging, to clinical, as in pulse oximetry. Despite the relatively low absorption of tissue in the near-infrared, there is still a significant amount of optical attenuation produced by the highly scattering nature of tissue. Because of this, designers of NIRS systems have to balance source optical power and source–detector separation to maximize the signal-to-noise ratio (SNR).

Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer.

Importance: Novel sensitive methods for detection and monitoring of residual disease can improve postoperative risk stratification with implications for patient selection for adjuvant chemotherapy (ACT), ACT duration, intensity of radiologic surveillance, and, ultimately, outcome for patients with colorectal cancer (CRC).

Objective: To investigate the association of circulating tumor DNA (ctDNA) with recurrence using longitudinal data from ultradeep sequencing of plasma cell-free DNA in patients with CRC before and after surgery, during and after ACT, and during surveillance.

Design, Setting, And Participants: In this prospective, multicenter cohort study, ctDNA was quantified in the preoperative and postoperative settings of stages I to III CRC by personalized multiplex, polymerase chain reaction-based, next-generation sequencing.