First-in-human evaluation of a hybrid modality that allows combined radio- and (near-infrared) fluorescence tracing during surgery.

PURPOSE: The clinical introduction of the hybrid tracer indocyanine green (ICG)-(99m)Tc-nanocolloid, composed of a radioactive and a near-infrared (NIR) fluorescence component, has created the need for surgical (imaging) modalities that allow for simultaneous detection of both signals. This study describes the first-in-human use of a prototype opto-nuclear probe during sentinel node (SN) biopsy using ICG-(99m)Tc-nanocolloid. METHODS: To allow for fluorescence tracing, a derivative of the conventional gamma probe technology was generated in which two optical fibers were integrated to allow for excitation (785 nm) and emission signal collection (> 810 nm). The ability of this opto-nuclear probe to detect the fluorescence signal of the hybrid tracer ICG-(99m)Tc-nanocolloid was firstly determined ex vivo in (non)SNs samples obtained from 41 patients who underwent hybrid tracer-based SN biopsy in the head and neck or urogenital area. In an in vivo proof-of-concept study in nine of these 41 patients, SNs were localized using combined gamma and fluorescence tracing with the opto-nuclear probe. Fluorescence tracing was performed in a similar manner as gamma tracing and under ambient light conditions. RESULTS: Ex vivo, the gamma tracing option of the opto-nuclear probe correctly identified the SN in all 150 evaluated (non)SN samples. Ex vivo fluorescence tracing in the low-sensitivity mode correctly identified 71.7% of the samples. This increased to 98.9% when fluorescence tracing was performed in the high-sensitivity mode. In vivo fluorescence tracing (high-sensitivity mode) accurately identified the SNs in all nine patients (20 SNs evaluated; 100%). CONCLUSION: This study demonstrates the first-in-human evaluation of a hybrid modality capable of detecting both gamma and fluorescence signals during a surgical procedure. Fluorescence tracing could be performed in ambient light.

[Risks associated with unrestricted consumption of alkaline-reduced water]. / Les risques d'une libre consommation d'eau réductrice alcaline produite par électrolyse.

Consumption of alkaline reduced water produced by domestic electrolysis devices was approved in Japan in 1965 by the Minister of Health, Work and Wellbeing, for the treatment of gastrointestinal disorders. Today, these devices are also freely available in France. The commercial information provided with the devices recommends the consumption of 1 to 1.5 liters per day, not only for gastrointestinal disorders but also for numerous other illnesses such as diabetes, cancer and inflammation. Academic research on this subject has been undergoing in Japan since 1990, and has established that the active ingredient is dissolved dihydrogen, which eliminates the free radical HO· in vivo. It has also been shown that electrode degradation during use of the devices releases highly reactive platinum nanoparticles, the toxicity of which is unknown. The authors of this report recommend alerting the French health authorities to the uncontrolled availability of these devices that generate drug substances and should therefore be subject to regulatory requirements.

Sentinel lymph nodes fluorescence detection and imaging using Patent Blue V bound to human serum albumin.

Patent Blue V (PBV), a dye used clinically for sentinel lymph node detection, was mixed with human serum albumin (HSA). After binding to HSA, the fluorescence quantum yield increased from 5 × 10(-4) to 1.7 × 10(-2), which was enough to allow fluorescence detection and imaging of its distribution. A detection threshold, evaluated in scattering test objects, lower than 2.5 nmol × L(-1) was obtained, using a single-probe setup with a 5-mW incident light power. The detection sensitivity using a fluorescence imaging device was in the µmol × L(-1) range, with a noncooled CCD camera. Preclinical evaluation was performed on a rat model and permitted to observe inflamed nodes on all animals.

Remyelination assessment by MRI texture analysis in a cuprizone mouse model.

The purpose of this study was to perform serial texture analysis of brain MRI of cuprizone-treated mice for the assessment of regional demyelination and remyelination. Cuprizone-fed mice undergo a brain demyelination process. This process was followed over 56 days by MRI in the olfactory bulbs, cerebellum, putamen and brain stem. The texture of T2-weighted images has been analyzed at two levels: (1) with the average intensity as first order parameter and (2) with several higher order parameters for the best differentiation between myelinated (controls) and demyelinated brains. The most pertinent of these parameters, called horizontal gray level nonuniformity (HGLNU), has been selected by stepwise discriminant analysis. The time evolution of the average value of HGLNU not only confirmed the overall demyelination tendency followed by the average intensity, but also more precisely characterized a transitory remyelination on day 41 in the olfactory bulbs and cerebellum, in agreement with already published immunohistochemical destructive studies.

Texture analysis of the brain: from animal models to human applications.

Magnetic resonance imaging (MRI) is widely used to image brain in vivo both in studies in animal models and for human diagnosis. A large part of the value of MRI is due to the fact that soft tissue contrast is enhanced by the substantial variation in the T(1) and T(2) relaxation times between tissues. It may be possible to use an alternative approach, which does not rely on the absolute measurement of relaxation times. Generally speaking, textures are complex visual patterns composed of entities, or subpatterns, that have characteristic brightness, color, slope, size, etc. Thus, texture can be regarded as a similarity grouping in an image. The properties of the local subpattern give rise to the perceived lightness, uniformity, density, roughness, regularity, linearity, frequency, phase, directionality, coarseness, randomness, fineness, smoothness, and granulation. The purpose here is to illustrate how texture analysis can be used in animal models and in human clinical applications, as well as in the search for further pharmacological applications in humans. Thus, this article summarzes three different MRI studies in (i) rats, using the lipocarpine epileptic rat model as an animal model; (ii) patients with Alzheimer's disease; and (iii) patients with schizophrenia.