Continuous function of 80 primary renal allografts for 30-47 years with maintenance prednisone and azathioprine/mycophenolate mofetil therapy: A clinical mosaic of long-term successes.

Eighty primary renal allograft recipients, 61 living-related and 19 deceased donor, transplanted from 1963 through 1984 had continuous graft function for 30-47 years. They were treated with three different early immunosuppression programs (1963-1970: thymectomy, splenectomy, high oral prednisone; 1971-1979: divided-dose intravenous methylprednisolone; and 1980-1984: antilymphocyte globulin) each with maintenance prednisone and azathioprine, and no calcineurin inhibitor. Long-term treatment often included the anti-platelet medication, dipyridamole. Although both recipient and donor ages were young (27.2 ± 9.5 and 33.1 ± 12.0 years, respectively), six recipients with a parent donor had >40-year success. At 35 years, death-censored graft survival was 85.3% and death with a functioning graft 84.2%; overall graft survival was 69.5% (Kaplan-Meier estimate). Biopsy-documented early acute cellular and highly probable antibody-mediated rejections were reversed with divided-dose intravenous methylprednisolone. Complications are detailed in an integrated timeline. Hypogammaglobulinemia identified after 20 years doubled the infection rate. An association between a monoclonal gammopathy of undetermined significance and non-plasma-cell malignancies was identified. Twenty-seven azathioprine-treated patients tested after 37 years had extremely low levels of T1/T2 B lymphocytes representing a "low immunosuppression state of allograft acceptance (LISAA)". The lifetime achievements of these patients following a single renal allograft and low-dose maintenance immunosuppression are remarkable. Their success evolved as a clinical mosaic.

Modeling passive millimeter wave imaging sensor performance for discriminating small watercraft.

Passive millimeter wave (pmmW) imagers are quickly becoming practical sensor candidates for military and nonmilitary tasks. Our focus was to adapt the Night Vision [U.S. Army Research Development and Engineering Command, Communications and Electronics Research Development and Engineering Center, Night Vision and Electronics Sensors Directorate (NVESD)] passive thermal infrared imager performance models and apply them to pmmW imaging systems for prediction of field performance for the task of small watercraft and boat identification. The Night Vision Lab's infrared sensor model has been evolving since the 1950s, with the most current model being NVThermIP [Night Vision Thermal and Image Processing (NVThermIP) Model Users Manual, Rev. 9 (U.S. Army RDECON, CERDEC, NVESD, 2006)]. It has wide recognition as an engineering tool for sensor evaluation. This effort included collecting pmmW signatures for a representative set of targets, conducting an observer perception experiment, and deriving the task difficulty criteria that can be used in NVThermIP for identification of boats. The task difficulty criteria are used by designers and managers to create systems capable of meeting specific performance criteria in the field.

Synthesis and evaluation of near-infrared (NIR) dye-herceptin conjugates as photoacoustic computed tomography (PCT) probes for HER2 expression in breast cancer.

We are evaluating PCT imaging in conjunction with NIR dye labeled Herceptin antibody for noninvasive assessment of HER2 expression in tumors. Herceptin was labeled with Alexa Fluor-750 amine reactive dye for characterization of photoacoustic and fluorescence signals. Measurements were performed in solution and after incubation in cultured cell lines that were positive or negative in expression of HER2. The dye to antibody ratio was controlled to achieve a broad range of degree of labeling (DOL = 2 to 15). Photoacoustic signal intensity of Herceptin-dye conjugates in solution increased with increases over the entire DOL range studied. In contrast, fluorescence exhibited significant quenching for higher DOL. In vitro PCT imaging of the labeled HER2 (+) and HER2 (-) cells revealed the targeting specificity of the NIR dye labeled Herceptin. In HER2 (+) cells lines, photoacoustic signal intensity gradually increased with increasing DOL and with increasing number of cells. These results demonstrate that PCT-based measurement of HER2 receptor binding using NIR dye labeled Herceptin is feasible. The absence of a quenching effect with increased DOL advantages this method over traditional methods based on fluorescence measurement.

Thermoacoustic computed tomography using a conventional linear transducer array.

We report on methodology for employing a conventional linear transducer array as a thermoacoustic detector in a thermoacoustic computed tomography (TCT) device, which has been designed for imaging small animals, e.g., athymic nude mice. We tested this concept using a 5 MHz, 128-element linear array (Acuson model L538). Thermoacoustic emissions were induced in a tissue-mimicking phantom using a Nd:YAg laser, operated at 1064 nm. Two-dimensional, axial "slice" images were formed using a filtered-backprojection algorithm. In-plane spatial resolution was measured as better than 200 microns with a slice thickness of 1.5 mm (full width at half maximum). The same detector, when operated as a conventional phased array, produced conventional ultrasound images in perfect registration with the TCT images.

Thermoacoustic molecular imaging of small animals.

We have designed, constructed, and tested a thermoacoustic computed tomography (TCT) scanner for imaging optical absorption in small animals in three dimensions. The device utilizes pulsed laser irradiation (680-1064 nm) and a unique, 128-element transducer array. We quantified the isotropic spatial resolution of this scanner to be 0.35 mm. We describe a dual-wavelength subtraction technique for isolating optical dyes with TCT. Phantom experiments demonstrate that we can detect 5 fmol of a near-infrared dye (indocyanine green, ICG) in a 1-microL volume using dual-wavelength subtraction. Initial TCT imaging in phantoms and in two sacrificed mice suggests that three-dimensional, optical absorption patterns in small animals can be detected with an order of magnitude better spatial resolution and an order of magnitude better low-contrast detectability in small animals when compared to fluorescence imaging or diffusion optical tomography.