Brian Catanzaro

Managing tissue heating in laser therapy to enable double-blind clinical study

Laser devices in clinical applications must eventually be tested via clinical trials. An essential component in clinical trials is the double-blind study whereby the patient and the treating physician have no knowledge as to whether a given treatment is active or placebo. In pharmaceuticals, the problem is easily addressed. With laser therapy this can be very challenging. For some optical therapies, laser heating of tissue, by even as little as a few degrees can indicate to the patient and/or the physician that the device is active, un-blinding the study. This problem has been analyzed for a specific laser therapy using a combination of clinical data, analytical methods, finite element modeling, and laboratory testing. The methods used arrived at a solution, but not necessarily one that could have been predicted easily. This paper will present a model of tissue heating and the methods used to mask the effects from the laser in an effort to make active treatment and placebo indistinguishable.

Review of technology development and clinical trials of transcranial laser therapy for acute ischemic stroke treatment

Stroke is the one of the leading causes of mortality in the United States, claiming 600,000 lives each year. Evidence suggests that near infrared (NIR) illumination has a beneficial effect on a variety of cells when these cells are exposed to adverse conditions. Among these conditions is the hypoxic state produced by acute ischemic stroke (AIS). To demonstrate the impact NIR Transcranial Laser Therapy (TLT) has on AIS in humans, a series of double blind, placebo controlled clinical trials were designed using the NeuroThera(R) System (NTS). The NTS was designed and developed to treat subjects non-invasively using 808 nm NIR illumination. TLT, as it applies to stroke therapy, and the NTS will be described. The results of the two clinical trials: NeuroThera(R) Safety and Efficacy Trial 1 (NEST-1) and NeuroThera(R) Safety and Efficacy Trial 2 (NEST-2) will be reviewed and discussed.

Rapid optical heating of blood for clinical point-of-care diagnostics

Clinical testing of human blood requires adherence to a number of regulatory standards, including maintaining a temperature that is representative of the human body (e.g. 37 C). The economics of private and public healthcare drives blood assays to be conducted using low cost, disposable assay devices that also eliminate the possibility of cross contamination. Unfortunately, the materials that meet the economic and disposable constraints of the marketplace are thermal insulators, not ideal for rapid heating. We present a novel means of optically heating blood samples in plastic assay devices within a time period suitable for point-of-care use. The novel approach uses LEDs in the red portion of the visible spectrum. The lower absorption of optical radiation in the visible spectrum enables the absorption of energy deep into the assay device. This produces even heating, avoiding the gradients that can occur by surface heating (conduction) or surface absorption (highly absorbing wavelengths). Analytical and computational models will be discussed. A specific application to a point-of-care blood assay instrument will be reviewed. In this application, optical heating was achieved using a small array of high brightness LEDs. Experimental results will be discussed. The experimental results with this instrument validated the predictions.

Mode field perturbations and numerical aperture broadening due to angular misalignment in multimode fiber coupling

Large core multimode fibers (MMF) in the range of 100-1000 μm core diameter are commonly used with infrared lasers in medical, bio-photonics and other fiber optics applications. Angular misalignment of the laser source to the multimode fiber can lead to unusual angular patterns at the exit of the fiber. The angular content of the launch beam can result in under-filling, non-uniform angular filling, or over-filling of the MMF modes. Typically, the beam condition optics at the distal end of the device has a limited impact on these angular modes. The result is often loss of output power at the distal end or an uncontrolled angular and/or spatial distribution of light. We have investigated angular misalignment perturbations of various fiber and coupling optics combinations in a medical laser therapy device. We have quantified the resulting far field perturbations, as well as the resulting broadening of the fiber output numerical aperture (NA). Angular misalignment may cause the development of so called donut modes with highly inhomogeneous far field mode distribution, as well as a substantial NA broadening effect which may impact therapy. We have shown that in order to avoid these perturbations, tight tolerancing of fiber coupling opto-mechanics as well as a thorough alignment procedure is required.

High-accuracy noncontact optical flow sensor for monitoring drug delivery

External and implantable infusion pumps are deployed in an ever widening variety of therapies. These devices are continually driven to increasing accuracy, smaller size, and lower cost. One opportunity for advancement in infusion pump technology is the improvement of closed loop monitoring of the delivery dosage of pharmaceuticals. An optical flow sensor has been designed, developed, and demonstrated based on a non-contact thermal time of flight architecture. The device is a diffraction based sensor. An analytical theory of operation will be presented. Simulations were conducted using a computational model based on heat transfer and computational fluid dymanics combined with diffraction optics calculations. These simulations were corroborated by experimental observations. The sensor has been demonstrated on several prototype platforms, including a prototype using telecommunications devices and packaging technology at a size of 20 mm x 20 mm x 5 mm. Experimental results will be presented demonstrating monitoring of flow rates between 240 nl/sec to 800 nL/sec with accuracies of better than 1% CV.