Bernhard B. Zimmermann

Functional brain imaging with a supercontinuum time-domain NIRS system

We have developed the second generation of our time-domain near-infrared spectroscopy (TD-NIRS) system for baseline and functional brain imaging. The instrument uses a pulsed broadband supercontinuum laser emitting a large spectrum between 650 and 1700 nm, and a gated detection based on an intensified CCD camera. The source laser beam is split into two arms, below and above 776 nm. In each arm, a fast motorized filter wheel enables selection of a bandpass filter at the required wavelength. Each filtered laser beam is then launched into one array of source fibers. The multiplexing through the array of fibers is implemented through a very compact home-made design consisting of two galvanometer mirrors followed by an achromatic doublet. Source fibers are then recombined one-by-one from both arms into the source optodes to be positioned on the head. The detection fibers are all imaged in parallel through a relay lens on an intensified CCD camera. By using detection fibers of different lengths, we introduce optical delays that enable simultaneous recording in different delay windows of the temporal point spread functions. We present the instrumentation and show its preliminary functional imaging capabilities. We also introduce a new probe where we use different fiber lengths on the source and the detector sides in order to record simultaneously both wavelengths from one location through different sets of fibers.

Multimodal breast cancer imaging using coregistered dynamic diffuse optical tomography and digital breast tomosynthesis

Abstract. Diffuse optical tomography (DOT) is emerging as a noninvasive functional imaging method for breast cancer diagnosis and neoadjuvant chemotherapy monitoring. In particular, the multimodal approach of combining DOT with x-ray digital breast tomosynthesis (DBT) is especially synergistic as DBT prior information can be used to enhance the DOT reconstruction. DOT, in turn, provides a functional information overlay onto the mammographic images, increasing sensitivity and specificity to cancer pathology. We describe a dynamic DOT apparatus designed for tight integration with commercial DBT scanners and providing a fast (up to 1 Hz) image acquisition rate to enable tracking hemodynamic changes induced by the mammographic breast compression. The system integrates 96 continuous-wave and 24 frequency-domain source locations as well as 32 continuous wave and 20 frequency-domain detection locations into low-profile plastic plates that can easily mate to the DBT compression paddle and x-ray detector cover, respectively. We demonstrate system performance using static and dynamic tissue-like phantoms as well as in vivo images acquired from the pool of patients recalled for breast biopsies at the Massachusetts General Hospital Breast Imaging Division.

Frequency domain near-infrared multiwavelength imager design using high-speed, direct analog-to-digital conversion

Abstract. Frequency domain near-infrared spectroscopy (FD-NIRS) has proven to be a reliable method for quantification of tissue absolute optical properties. We present a full-sampling direct analog-to-digital conversion FD-NIR imager. While we developed this instrument with a focus on high-speed optical breast tomographic imaging, the proposed design is suitable for a wide-range of biophotonic applications where fast, accurate quantification of absolute optical properties is needed. Simultaneous dual wavelength operation at 685 and 830 nm is achieved by concurrent 67.5 and 75 MHz frequency modulation of each laser source, respectively, followed by digitization using a high-speed (180  MS/s) 16-bit A/D converter and hybrid FPGA-assisted demodulation. The instrument supports 25 source locations and features 20 concurrently operating detectors. The noise floor of the instrument was measured at <1.4  pW/√Hz, and a dynamic range of 115+ dB, corresponding to nearly six orders of magnitude, has been demonstrated. Titration experiments consisting of 200 different absorption and scattering values were conducted to demonstrate accurate optical property quantification over the entire range of physiologically expected values.

Development and characterization of a multidistance and multiwavelength diffuse correlation spectroscopy system

Abstract. This paper presents a multidistance and multiwavelength diffuse correlation spectroscopy (DCS) approach and its implementation to simultaneously measure the optical proprieties of deep tissue as well as the blood flow. The system consists of three long coherence length lasers at different wavelengths in the near-infrared, eight single-photon detectors, and a correlator board. With this approach, we collect both light intensity and DCS data at multiple distances and multiple wavelengths, which provide unique information to fit for all the parameters of interest: scattering, blood flow, and hemoglobin concentration. We present the characterization of the system and its validation with phantom measurements.

Fast diffuse correlation spectroscopy (DCS) for non-invasive measurement of intracranial pressure (ICP) (Conference Presentation)

Intracranial pressure (ICP) monitoring has a key role in the management of neurosurgical and neurological injuries. Currently, the standard clinical monitoring of ICP requires an invasive transducer into the parenchymal tissue or the brain ventricle, with possibility of complications such as hemorrhage and infection. A non-invasive method for measuring ICP, would be highly preferable, as it would allow clinicians to promptly monitor ICP during transport and allow for monitoring in a larger number of patients. We have introduced diffuse correlation spectroscopy (DCS) as a non-invasive ICP monitor by fast measurement of pulsatile cerebral blood flow (CBF). The method is similar to Transcranial Doppler ultrasound (TCD), which derives ICP from the amplitude of the pulsatile cerebral blood flow velocity, with respect to the amplitude of the pulsatile arterial blood pressure. We believe DCS measurement is superior indicator of ICP than TCD estimation because DCS directly measures blood flow, not blood flow velocity, and the small cortical vessels measured by DCS are more susceptible to transmural pressure changes than the large vessels. For fast DCS measurements to recover pulsatile CBF we have developed a custom high-power long-coherent laser and a strategy for delivering it to the tissue within ANSI standards. We have also developed a custom FPGA-based correlator board, which facilitates DCS data acquisitions at 50-100 Hz. We have tested the feasibility of measuring pulsatile CBF and deriving ICP in two challenging scenarios: humans and rats. SNR is low in human adults due to large optode distances. It is similarly low in rats because the fast heart rate in this setting requires a high repetition rate.

A Novel Tomographic Optical Breast Imaging System to Simultaneously Co-Register X-Ray Tomosynthesis

We constructed a novel tomographic optical breast imager with simultaneous x-ray tomosynthesis co-registration. It consists of a continuous wave and a frequency encoded frequency domain imaging unit connected to an x-ray translucent fiber optic probe.