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Subcellular spatial resolution achieved for deep-brain imaging in vivo using a minimally invasive multimode fiber.

ABSTRACT: Achieving intravital optical imaging with diffraction-limited spatial resolution of deep-brain structures represents an important step toward the goal of understanding the mammalian central nervous system^1-4. Advances in wavefront-shaping methods and computational power have recently allowed for a novel approach to high-resolution imaging, utilizing deterministic light propagation through optically complex media and, of particular importance for this work, multimode optical fibers (MMFs)^5-7. We report a compact and highly optimized approach for minimally invasive in vivo brain imaging applications. The volume of tissue lesion was reduced by more than 100-fold, while preserving diffraction-limited imaging performance utilizing wavefront control of light propagation through a single 50-μm-core MMF. Here, we demonstrated high-resolution fluorescence imaging of subcellular neuronal structures, dendrites and synaptic specializations, in deep-brain regions of living mice, as well as monitored stimulus-driven functional Ca²⁺ responses. These results represent a major breakthrough in the compromise between high-resolution imaging and tissue damage, heralding new possibilities for deep-brain imaging in vivo.

SUBMITTER: Vasquez-Lopez SA

PROVIDER: S-EPMC6298975 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:SIGNIFICANCE:Noninvasive in vivo fast pulsatile blood flow measurement in deep tissue is important because the blood flow waveform is correlated with physiological parameters, such as blood pressure and elasticity of blood vessels. Compromised blood flow may cause diseases, such as stroke, foot ulcer, and myocardial ischemia. There is great clinical demand for a portable and cost-effective device for noninvasive pulsatile blood flow measurement. AIM:A diffuse-optics-based method, diffuse speckle pulsatile flowmetry (DSPF), was developed for fast measurement (?300??Hz) of deep tissue blood flow noninvasively. To validate its performance, both a phantom experiment and in vivo demonstration were conducted. APPROACH:Over the past two decades, single-mode fibers have been used as detection fibers in most diffuse-optics-based deep tissue blood flow measurement modalities. We used a multimode (MM) detection fiber with a core size of 200???m for diffused speckle pattern detection. A background intensity correction algorithm was implemented for speckle contrast calculation. The MM detection fiber helped to achieve a level of deep tissue blood flow measurement similar to that of conventional modalities, such as diffuse correlation spectroscopy and diffuse speckle contrast analysis, but it increases the measurement rate of blood flow to 300 Hz. RESULTS:The design and implementation of the DSPF system were introduced. The theory of the background intensity correction for the diffused speckle pattern detected by the MM fiber was explained. A flow phantom was built for validation of the performance of the DSPF system. An in vivo cuff-induced occlusion experiment was performed to demonstrate the capability of the proposed DSPF system. CONCLUSIONS:An MM detection fiber can help to achieve fast (?300??Hz) pulsatile blood flow measurement in the proposed DSPF method. The cost-effective device and the fiber-based flexible probe increase the usability of the DSPF system significantly.

Project description:Purpose To develop and demonstrate in vitro and in vivo a single interventional magnetic resonance (MR)-active device that integrates the functions of precise identification of a tissue site with the delivery of radiofrequency (RF) energy for ablation, high-spatial-resolution thermal mapping to monitor thermal dose, and quantitative MR imaging relaxometry to document ablation-induced tissue changes for characterizing ablated tissue. Materials and Methods All animal studies were approved by the institutional animal care and use committee. A loopless MR imaging antenna composed of a tuned microcable either 0.8 or 2.2 mm in diameter with an extended central conductor was switched between a 3-T MR imaging unit and an RF power source to monitor and perform RF ablation in bovine muscle and human artery samples in vitro and in rabbits in vivo. High-spatial-resolution (250-300-μm) proton resonance frequency shift MR thermometry was interleaved with ablations. Quantitative spin-lattice (T1) and spin-spin (T2) relaxation time MR imaging mapping was performed before and after ablation. These maps were compared with findings from gross tissue examination of the region of ablated tissue after MR imaging. Results High-spatial-resolution MR imaging afforded temperature mapping in less than 8 seconds for monitoring ablation temperatures in excess of 85°C delivered by the same device. This produced irreversible thermal injury and necrosis. Quantitative MR imaging relaxation time maps demonstrated up to a twofold variation in mean regional T1 and T2 after ablation versus before ablation. Conclusion A simple, integrated, minimally invasive interventional probe that provides image-guided therapy delivery, thermal mapping of dose, and detection of ablation-associated MR imaging parametric changes was developed and demonstrated. With this single-device approach, coupling-related safety concerns associated with multiple conductor approaches were avoided. © RSNA, 2016 Online supplemental material is available for this article.

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Subcellular spatial resolution achieved for deep-brain imaging in vivo using a minimally invasive multimode fiber.

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