Debbie K. Chen

NEAR-INFRARED, BROAD-BAND SPECTRAL IMAGING OF THE HUMAN BREAST FOR QUANTITATIVE OXIMETRY: APPLICATIONS TO HEALTHY AND CANCEROUS BREASTS

We have examined ten human subjects with a previously developed instrument for near-infrared diffuse spectral imaging of the female breast. The instrument is based on a tandem, planar scan of two collinear optical fibers (one for illumination and one for collection) to image a gently compressed breast in a transmission geometry. The optical data collection features a spatial sampling of 25 points/cm2 over the whole breast, and a spectral sampling of 2 points/nm in the 650–900 nm wavelength range. Of the ten human subjects examined, eight are healthy subjects and two are cancer patients with unilateral invasive ductal carcinoma and ductal carcinoma in situ, respectively. For each subject, we generate second-derivative images that identify a network of highly absorbing structures in the breast that we assign to blood vessels. A previously developed paired-wavelength spectral method assigns oxygenation values to the absorbing structures displayed in the second-derivative images. The resulting oxygenation images feature average values over the whole breast that are significantly lower in cancerous breasts (69 ± 14%, n = 2) than in healthy breasts (85 ± 7%, n = 18) (p < 0.01). Furthermore, in the two patients with breast cancer, the average oxygenation values in the cancerous regions are also significantly lower than in the remainder of the breast (invasive ductal carcinoma: 49 ± 11% vs 61 ± 16%, p < 0.01; ductal carcinoma in situ: 58 ± 8% vs 77 ± 11%, p < 0.001).

Spectral and spatial dependence of diffuse optical signals in response to peripheral nerve stimulation

Using non-invasive, near-infrared spectroscopy we have previously reported optical signals measured at or around peripheral nerves in response to their stimulation. Such optical signals featured amplitudes on the order of 0.1% and peaked about 100 ms after peripheral nerve stimulation in human subjects. Here, we report a study of the spatial and spectral dependence of the optical signals induced by stimulation of the human median and sural nerves, and observe that these optical signals are: (1) unlikely due to either dilation or constriction of blood vessels, (2) not associated with capillary bed hemoglobin, (3) likely due to blood vessel(s) displacement, and (4) unlikely due to fiber-skin optical coupling effects. We conclude that the most probable origin of the optical response to peripheral nerve stimulation is from displacement of blood vessels within the optically probed volume, as a result of muscle twitch in adjacent areas.

Diffuse optical signals in response to peripheral nerve stimulation reflect skeletal muscle kinematics

Previously we have reported a near-infrared optical response in the region occupied by a peripheral nerve that is distal to the site of electrical stimulation of that peripheral nerve. This “intermediate” signal is vascular in nature but its biological origin not been elucidated. In the present study, an animal model of the signal has been created and our human studies expanded to directly investigate the contribution of non-artifactual vascular motion induced by muscle contraction to the biological origin of this signal. Under non-invasive conditions during stimulation of the exposed sciatic nerve of the Sprague-Dawley rat, optical responses are robust. These signals can be abolished both pharmacologically and surgically using methods that eliminate muscle motion while leaving the electrophysiological health of the nerve intact. In human studies, signals that are elicited on stimulation of nerves containing motor axons, both within and outside the predicted imaging volume of the spectrometer, have similar temporal characteristics of those previously observed. Moreover, stimulation of sensory nerves alone does not elicit an optical response. These results strongly suggest that the intermediate signals are derived from stimulus-induced muscle contraction (whether via an innervating nerve or by direct stimulation) causing translational vascular motion within the optically interrogated region.

Near-infrared signals associated with electrical stimulation of peripheral nerves

We report our studies on the optical signals measured non-invasively on electrically stimulated peripheral nerves. The stimulation consists of the delivery of 0.1 ms current pulses, below the threshold for triggering any visible motion, to a peripheral nerve in human subjects (we have studied the sural nerve and the median nerve). In response to electrical stimulation, we observe an optical signal that peaks at about 100 ms post-stimulus, on a much longer time scale than the few milliseconds duration of the electrical response, or sensory nerve action potential (SNAP). While the 100 ms optical signal we measured is not a direct optical signature of neural activation, it is nevertheless indicative of a mediated response to neural activation. We argue that this may provide information useful for understanding the origin of the fast optical signal (also on a 100 ms time scale) that has been measured non-invasively in the brain in response to cerebral activation. Furthermore, the optical response to peripheral nerve activation may be developed into a diagnostic tool for peripheral neuropathies, as suggested by the delayed optical signals (average peak time: 230 ms) measured in patients with diabetic neuropathy with respect to normal subjects (average peak time: 160 ms).

Fast optical response to electrical activation in peripheral nerves

Complex neuronal structures and interactions make studying fast optical signals associated with brain activation difficult, especially in non-invasive measurements that are further complicated by the filtering effect of the scalp and skull. We have chosen to study fast optical signals in the peripheral nervous system to look at a more simplified biological neuronal structure and a system that is more accessible to non-invasive optical studies. In this study, we recorded spatially resolved electrical and optical responses of the human sural nerve to electrical stimulation. A 0.1 ms electrical stimulation was used to activate the sural nerve. Electrical signals were collected by an electromyogram machine and results showed an electrical response spanning a distance of 8 mm across the nerve. Optical signals were collected by a two-wavelength (690 and 830 nm) near-infrared spectrometer and displayed a characteristic decrease in intensity at both wavelengths. Data were taken at multiple positions and then reproduced five times. The average optical data over the five trials showed an optical signal that was spatially consistent with the electrical response to sural nerve stimulation.

Electrical stimulation of peripheral nerves induces optical responses via skeletal muscle kinematics

We have previously reported an optical response in human subjects occurring at 100 ms following electrical stimulation of peripheral nerves. In the present study, an animal model has been created to directly investigate the myogenic components of the signal. In addition, experiments have been performed in human subjects to investigate the signals neuroanatomical specificity, sensitivity to muscle motion, and spatial and spectral features. The results of this work suggest that the observed optical signal derives from stimulus-induced motion associated with muscle contraction and likely contains myological information of clinical value.

In vivo Applications of Diffuse Optical Imaging and Spectroscopy

This contribution reviews some of the concepts of diffuse optical imaging and spectroscopy of tissue, and presents some in vivo applications to the human breast (optical mammography) and brain (functional near-infrared imaging).

Non-Invasive Optical Response to Electrical Stimulation in Peripheral Nerves

We report non-invasive optical measurements on the sural nerve of a human subject during electrical stimulation. We observed a fast optical response (time scale of 10-100 ms) associated with electrical stimulation of the nerve.