Cot-side imaging of functional connectivity in the developing brain during sleep using wearable high-density diffuse optical tomography.

Studies of cortical function in newborn infants in clinical settings are extremely challenging to undertake with traditional neuroimaging approaches. Partly in response to this challenge, functional near-infrared spectroscopy (fNIRS) has become an increasingly common clinical research tool but has significant limitations including a low spatial resolution and poor depth specificity. Moreover, the bulky optical fibres required in traditional fNIRS approaches present significant mechanical challenges, particularly for the study of vulnerable newborn infants. A new generation of wearable, modular, high-density diffuse optical tomography (HD-DOT) technologies has recently emerged that overcomes many of the limitations of traditional, fibre-based and low-density fNIRS measurements. Driven by the development of this new technology, we have undertaken the first cot-side study of newborn infants using wearable HD-DOT in a clinical setting. We use this technology to study functional brain connectivity (FC) in newborn infants during sleep and assess the effect of neonatal sleep states, active sleep (AS) and quiet sleep (QS), on resting state FC. Our results demonstrate that it is now possible to obtain high-quality functional images of the neonatal brain in the clinical setting with few constraints. Our results also suggest that sleep states differentially affect FC in the neonatal brain, consistent with prior reports.

Quality assurance in proton beam therapy using a plastic scintillator and a commercially available digital camera.

PURPOSE: In this article, we evaluate a plastic scintillation detector system for quality assurance in proton therapy using a BC-408 plastic scintillator, a commercial camera, and a computer. METHODS: The basic characteristics of the system were assessed in a series of proton irradiations. The reproducibility and response to changes of dose, dose-rate, and proton energy were determined. Photographs of the scintillation light distributions were acquired, and compared with Geant4 Monte Carlo simulations and with depth-dose curves measured with an ionization chamber. A quenching effect was observed at the Bragg peak of the 60 MeV proton beam where less light was produced than expected. We developed an approach using Birks equation to correct for this quenching. We simulated the linear energy transfer (LET) as a function of depth in Geant4 and found Birks constant by comparing the calculated LET and measured scintillation light distribution. We then used the derived value of Birks constant to correct the measured scintillation light distribution for quenching using Geant4. RESULTS: The corrected light output from the scintillator increased linearly with dose. The system is stable and offers short-term reproducibility to within 0.80%. No dose rate dependency was observed in this work. CONCLUSIONS: This approach offers an effective way to correct for quenching, and could provide a method for rapid, convenient, routine quality assurance for clinical proton beams. Furthermore, the system has the advantage of providing 2D visualization of individual radiation fields, with potential application for quality assurance of complex, time-varying fields.

Development of a near infrared multi-wavelength, multi-channel, time-resolved spectrometer for measuring brain tissue haemodynamics and metabolism.

We present a novel time domain functional near infrared spectroscopy system using a supercontinuum laser allowing us to measure the coefficient of absorption and scattering of up to 16 multiplexed wavelengths in the near infrared region. This is a four detector system that generates up to 3 mW of light for each wavelength with a narrow 2-3 nm FWHM bandwidth between 650 and 890 nm; each measurement of 16 wavelengths per channel can be performed up to a rate of 1 Hz. We can therefore quantify absolute haemoglobin changes in tissue and are currently investigating which and how many wavelengths are needed to resolve additional chromophores in tissue, such as water and the oxidation state of cytochrome-c-oxidase.

Monitoring the response to neoadjuvant hormone therapy for locally advanced breast cancer using three-dimensional time-resolved optical mammography.

Optical mammography is a functional imaging technique that uses near-infrared light to produce three-dimensional breast images of tissue oxygen saturation and hemoglobin concentration. It has been used to monitor the response to neoadjuvant chemotherapy in breast cancer patients. We present the first results on monitoring tumor response to hormone therapy using optical mammography. We present three case studies from postmenopausal women treated with neoadjuvant hormone therapy for locally advanced breast cancer. The women were scanned before starting treatment, once during treatment, and then before surgery. Changes in physiological and optical properties within the tumor and in the rest of the breast were evaluated. At the time of surgery, two patients partially responded to treatment and one did not respond. The patients that partially responded on ultrasound revealed a corresponding recovery to normal in the hemoglobin concentration images, whereas the nonresponder indicated an increase in hemoglobin concentration in the tumor compared to her pretreatment images. These case studies suggest that optical imaging of the breast during neoadjuvant hormone treatment can provide potentially valuable information, and that physiological changes within the tumor can be seen in response to treatment.

Diffuse optical imaging of the healthy and diseased breast: a systematic review.

Screening X-ray mammography is limited by false positives and negatives leading to unnecessary physical and psychological morbidity. Diffuse Optical Imaging using harmless near infra red light, provides lesion detection based on functional abnormalities and represents a novel diagnostic arm that could complement traditional mammography. Reviews of optical breast imaging have not been systematic, are focused mainly on technological developments, and have become superseded by rapid technological advancement. The aim of this study is to review clinically orientated studies involving approximately 2,000 women in whom optical mammography has been used to evaluate the healthy or diseased breast. The results suggest that approximately 85% of breast lesions are detectable on optical mammography. Spectroscopic resolution of tissue haemoglobin composition and oxygen saturation may improve the detectability of breast diseases. Results suggest that breast lesions contain approximately twice the haemoglobin concentration of background tissue. Current evidence suggests that it is not possible to distinguish benign from malignant disease using optical imaging techniques in isolation. Methods to improve the performance of Diffuse Optical Imaging, such as better spectral coverage with additional wavelengths, improved modelling of light transport in tissues and the use of extrinsic dyes may augment lesion detection and characterisation. Future research should involve large clinical trials to determine the overall sensitivity and specificity of optical imaging techniques as well as to establish patient satisfaction and economic viability.