Ultimate resolution limits of speckle-based compressive imaging.

Compressive imaging using sparsity constraints is a very promising field of microscopy that provides a dramatic enhancement of the spatial resolution beyond the Abbe diffraction limit. Moreover, it simultaneously overcomes the Nyquist limit by reconstructing an N-pixel image from less than N single-point measurements. Here we present fundamental resolution limits of noiseless compressive imaging via sparsity constraints, speckle illumination and single-pixel detection. We addressed the experimental setup that uses randomly generated speckle patterns (in a scattering media or a multimode fiber). The optimal number of measurements, the ultimate spatial resolution limit and the surprisingly important role of discretization are demonstrated by the theoretical analysis and numerical simulations. We show that, in contrast to conventional microscopy, oversampling may decrease the resolution and reconstruction quality of compressive imaging.

The search for a unique Raman signature of amyloid-beta plaques in human brain tissue from Alzheimer's disease patients.

Definite Alzheimer's disease (AD) diagnosis is commonly done on ex vivo brain tissue using immuno-histochemical staining to visualize amyloid-beta (Aß) aggregates, also known as Aß plaques. Raman spectroscopy has shown its potential for non-invasive and label-free determination of bio-molecular compositions, aiding the post-mortem diagnosis of pathological tissue. Here, we investigated whether conventional Raman spectroscopy could be used for the detection of amyloid beta deposits in fixed, ex vivo human brain tissue, taken from the frontal cortex region. We examined the spectra and spectral maps of three severe AD cases and two healthy control cases and compared their spectral outcome among each other as well as to recent results in the literature obtained with various spectroscopic techniques. After hyperspectral Raman mapping, Aß plaques were visualized using Thioflavin-S staining on the exact same tissue sections. As a result, we show that tiny diffuse or tangled-like morphological structures, visible under microscopic conditions on unstained tissue and often but erroneously assumed to be deposits of Aß, are instead usually an aggregation of highly auto-fluorescent lipofuscin granulates without any, or limited, plaque or plaque-like association. The occurrence of these auto-fluorescent particles is equally distributed in both AD and healthy control cases. Therefore, they cannot be used as possible criteria for Alzheimer's disease diagnosis. Furthermore, a unique plaque-specific/Aß spectrum could not be determined even after possible spectral interferences were carefully removed.

Performance evaluation of a two detector camera for real-time video.

Single pixel imaging can be the preferred method over traditional 2D-array imaging in spectral ranges where conventional cameras are not available. However, when it comes to real-time video imaging, single pixel imaging cannot compete with the framerates of conventional cameras, especially when high-resolution images are desired. Here we evaluate the performance of an imaging approach using two detectors simultaneously. First, we present theoretical results on how low SNR affects final image quality followed by experimentally determined results. Obtained video framerates were doubled compared to state of the art systems, resulting in a framerate from 22 Hz for a 32×32 resolution to 0.75 Hz for a 128×128 resolution image. Additionally, the two detector imaging technique enables the acquisition of images with a resolution of 256×256 in less than 3 s.

Swept-source multimode fiber imaging.

High-resolution compressive imaging via a flexible multimode fiber is demonstrated using a swept-laser source and wavelength dependent speckle illumination. An in-house built swept-source allowing for independent control of bandwidth and scanning range is used to explore and demonstrate a mechanically scan-free approach for high-resolution imaging through an ultrathin and flexible fiber probe. The computational image reconstruction is shown by utilizing a narrow sweeping bandwidth of [Formula: see text] nm while acquisition time is decreased by 95% compared to conventional raster scanning endoscopy. Demonstrated narrow-band illumination in the visible spectrum is vital for the detection of fluorescence biomarkers in neuroimaging applications. The proposed approach yields device simplicity and flexibility for minimally invasive endoscopy.

No difference in retinal fluorescence after oral curcumin intake in amyloid-proven AD cases compared to controls.

Introduction: Previous work has showed the in vivo presence of retinal amyloid in Alzheimer's disease (AD) patients using curcumin. We aimed to replicate these findings in an amyloid biomarker-confirmed cohort. Methods: Twenty-six patients with AD (age 66 [+9], Mini-Mental Status Examination [MMSE] ≥17) and 14 controls (age 71 [+12]) used one of three curcumin formulations: Longvida, Theracurmin, and Novasol. Plasma levels were determined and pre- and post-curcumin retinal fluorescence scans were assessed visually in all cases and quantitatively assessed in a subset. Results: Visual assessment showed no difference between AD patients and controls for pre- and post-curcumin images. This was confirmed by quantitative analyses on a subset. Mean conjugated plasma curcumin levels were 198.7 nM (Longvida), 576.6 nM (Theracurmin), and 1605.8 nM (Novasol). Discussion: We found no difference in retinal fluorescence between amyloid-confirmed AD cases and control participants, using Longvida and two additional curcumin formulations. Additional replication studies in amyloid-confirmed cohorts are needed to assess the diagnostic value of retinal fluorescence as an AD biomarker.

Multimodal, label-free fluorescence and Raman imaging of amyloid deposits in snap-frozen Alzheimer's disease human brain tissue.

Alzheimer's disease (AD) neuropathology is characterized by hyperphosphorylated tau containing neurofibrillary tangles and amyloid-beta (Aß) plaques. Normally these hallmarks are studied by (immuno-) histological techniques requiring chemical pretreatment and indirect labelling. Label-free imaging enables one to visualize normal tissue and pathology in its native form. Therefore, these techniques could contribute to a better understanding of the disease. Here, we present a comprehensive study of high-resolution fluorescence imaging (before and after staining) and spectroscopic modalities (Raman mapping under pre-resonance conditions and stimulated Raman scattering (SRS)) of amyloid deposits in snap-frozen AD human brain tissue. We performed fluorescence and spectroscopic imaging and subsequent thioflavin-S staining of the same tissue slices to provide direct confirmation of plaque location and correlation of spectroscopic biomarkers with plaque morphology; differences were observed between cored and fibrillar plaques. The SRS results showed a protein peak shift towards the ß-sheet structure in cored amyloid deposits. In the Raman maps recorded with 532 nm excitation we identified the presence of carotenoids as a unique marker to differentiate between a cored amyloid plaque area versus a non-plaque area without prior knowledge of their location. The observed presence of carotenoids suggests a distinct neuroinflammatory response to misfolded protein accumulations.

In vivo subdiffuse scanning laser oximetry of the human retina.

Scanning laser ophthalmoscopes (SLOs) have the potential to perform high speed, high contrast, functional imaging of the human retina for diagnosis and follow-up of retinal diseases. Commercial SLOs typically use a monochromatic laser source or a superluminescent diode for imaging. Multispectral SLOs using an array of laser sources for spectral imaging have been demonstrated in research settings, with applications mainly aiming at retinal oxygenation measurements. Previous SLO-based oximetry techniques are predominantly based on wavelengths that depend on laser source availability. We describe an SLO system based on a supercontinuum (SC) source and a double-clad fiber using the single-mode core for illumination and the larger inner cladding for quasi-confocal detection to increase throughput and signal-to-noise ratio. A balanced detection scheme was implemented to suppress the relative intensity noise of the SC source. The SLO produced dual wavelength, high-quality images at 10 frames / s with a maximum 20 deg imaging field-of-view with any desired combination of wavelengths in the visible spectrum. We demonstrate SLO-based dual-wavelength oximetry in vessels down to 50 µm in diameter. Reproducibility was demonstrated by performing three different imaging sessions of the same volunteer, 8 min apart. Finally, by performing a wavelength sweep between 485 and 608 nm, we determined, for our SLO geometry, an approximately linear relationship between the effective path length of photons through the blood vessels and the vessel diameter.