Super-Resolution and Wide-Field-of-View Imaging Based on Large-Angle Deflection with Risley Prisms.

A novel single camera combined with Risley prisms is proposed to achieve a super-resolution (SR) imaging and field-of-view extension (FOV) imaging method. We develop a mathematical model to consider the imaging aberrations caused by large-angle beam deflection and propose an SR reconstruction scheme that uses a beam backtracking method for image correction combined with a sub-pixel shift alignment technique. For the FOV extension, we provide a new scheme for the scanning position path of the Risley prisms and the number of image acquisitions, which improves the acquisition efficiency and reduces the complexity of image stitching. Simulation results show that the method can increase the image resolution to the diffraction limit of the optical system for imaging systems where the resolution is limited by the pixel size. Experimental results and analytical verification yield that the resolution of the image can be improved by a factor of 2.5, and the FOV extended by a factor of 3 at a reconstruction factor of 5. The FOV extension is in general agreement with the simulation results. Risley prisms can provide a more general, low-cost, and efficient method for SR reconstruction, FOV expansion, central concave imaging, and various scanning imaging.

Diffuse optical detection of global cerebral ischemia in an adult porcine model.

Rapid screening for ischemic strokes in prehospital settings may improve patient outcomes by allowing early deployment of vascular recanalization therapies. However, there are no low-cost and convenient methods that can assess ischemic strokes in such a setting. Diffuse correlation spectroscopy (DCS) is a promising method for continuous, noninvasive transcranial monitoring of cerebral blood flow. In this study, we used a DCS system to detect cerebral hemodynamics before and after acute ischemic stroke in pigs. Seven adult porcines were chosen to establish ischemic stroke models via bilateral common carotid artery ligation (n = 5) or air emboli (n = 2). The results showed a significant difference in blood flow index (BFI) between the normal and ischemic groups. Relative blood flow index (rBFI) exhibited excellent results. Therefore, the diffuse optical method can assess the hemodynamic changes in acute cerebral ischemic stroke onset in pigs, and rBFI may be a promising biomarker for identifying cerebral ischemic stroke.

Influence of probe pressure on the pulsatile diffuse correlation spectroscopy blood flow signal on the forearm and forehead regions.

In a pilot study of 11 healthy adults (24 to 39 years, all male), we characterize the influence of external probe pressure on optical diffuse correlation spectroscopy (DCS) measurements of pulsatile blood flow obtained on the forearm and forehead. For external probe pressure control, a hand inflatable air balloon is inserted between the tissue and an elastic strap. The air balloon is sequentially inflated to achieve a wide range of external probe pressures between 20 and 250 mmHg on the forearm and forehead, which are measured with a flexible pressure sensor underneath the probe. At each probe pressure, the pulsatility index (PI) of arteriole blood flow on the forehead and forearm is measured with DCS (2.1-cm source-detector separation). We observe a strong correlation between probe pressure and PI on the forearm ( R = 0.66 , p < 0.001 ), but not on the forehead ( R = - 0.11 , p = 0.4 ). The forearm measurements demonstrate the sensitivity of the DCS PI to skeletal muscle tissue pressure, whereas the forehead measurements indicate that DCS PI measurements are not sensitive to scalp tissue pressure. Note, in contrast to pulsatility, the time-averaged DCS blood flow index on the forehead was significantly correlated with probe pressure ( R = - 0.55 , p < 0.001 ). This pilot data appears to support the initiation of more comprehensive clinical studies on DCS to detect trends in internal pressure in brain and skeletal muscle.

Bi-fiber quasi-axis probe for photonic Doppler velocimetry for shock physics experiments.

Photonic Doppler velocimetry (PDV) has become a major domain velocity measurement technique for shock physics experiments. In this study, we propose and validate a bi-fiber quasi-axis probe for PDV that consists of a multimode source fiber and a single-mode detection fiber. This structure makes the received light by the probe totally reflected or scattered from the target, and, therefore, is free from the influence of unwanted return light. The light-receiving efficiency of the probe was calculated by the Monte Carlo method and was validated by static experiment. We validate that the feasibility of probe by dynamic experiments with measurement depth up to 6 cm. Above all, the bi-fiber quasi-axis probe is a promising supplementary probe for PDV for shock physics experiments.

Purified frequency modulation of a quantum cascade laser with an all-optical approach.

Purified frequency modulation (FM) is demonstrated in a standard middle-infrared quantum cascade laser by illuminating its front facet with two near-infrared (NIR) lasers. A 2 mW laser at 1550 nm is utilized to modulate the amplitude and frequency of a quantum cascade laser, and the associated amplitude modulation (AM) is suppressed by a 1.85 mW laser at 850 nm. Due to the hot carrier effect and the increment of electron temperature, the AM has been decreased. In addition, the free carrier concentration increases in the active region due to the two NIR illuminations, which enhance the FM. Purified FM is beneficial in improving the signal fidelity for free-space optical communication and high-speed FM spectroscopy.

Fast blood flow monitoring in deep tissues with real-time software correlators.

We introduce, validate and demonstrate a new software correlator for high-speed measurement of blood flow in deep tissues based on diffuse correlation spectroscopy (DCS). The software correlator scheme employs standard PC-based data acquisition boards to measure temporal intensity autocorrelation functions continuously at 50 - 100 Hz, the fastest blood flow measurements reported with DCS to date. The data streams, obtained in vivo for typical source-detector separations of 2.5 cm, easily resolve pulsatile heart-beat fluctuations in blood flow which were previously considered to be noise. We employ the device to separate tissue blood flow from tissue absorption/scattering dynamics and thereby show that the origin of the pulsatile DCS signal is primarily flow, and we monitor cerebral autoregulation dynamics in healthy volunteers more accurately than with traditional instrumentation as a result of increased data acquisition rates. Finally, we characterize measurement signal-to-noise ratio and identify count rate and averaging parameters needed for optimal performance.

Calibration of diffuse correlation spectroscopy blood flow index with venous-occlusion diffuse optical spectroscopy in skeletal muscle.

We investigate and assess the utility of a simple scheme for continuous absolute blood flow monitoring based on diffuse correlation spectroscopy (DCS). The scheme calibrates DCS using venous-occlusion diffuse optical spectroscopy (VO-DOS) measurements of arm muscle tissue at a single time-point. A calibration coefficient (γ) for the arm is determined, permitting conversion of DCS blood flow indices to absolute blood flow units, and a study of healthy adults (N=10) is carried out to ascertain the variability of γ. The average DCS calibration coefficient for the right (i.e., dominant) arm was γ=(1.24±0.15)×10(8) (mL·100 mL(−1)·min(−1))/(cm(2)/s). However, variability can be significant and is apparent in our site-to-site and day-to-day repeated measurements. The peak hyperemic blood flow overshoot relative to baseline resting flow was also studied following arm-cuff ischemia; excellent agreement between VO-DOS and DCS was found (R(2)=0.95, slope=0.94±0.07, mean difference=−0.10±0.45). Finally, we show that incorporation of subject-specific absolute optical properties significantly improves blood flow calibration accuracy.

A novel photonic Doppler velocimetry for transverse velocity measurement.

A fiber interferometry for transverse velocity measurement has been developed. This diagnostic is similar to photonic Doppler velocimetry in the way in which laser propagates and couples. The interferometer mainly consists of a fiber coupler, an emitting probe, and two receiving probes. A pair of scattered laser beams mix in the coupler and generates fringes with frequency proportional to transverse velocity. Measurement of transverse velocity is independent of longitudinal velocity. The feasibility of the technique has been verified by rotating wheel experiment and shock loading experiment.

Inactivation of mammalian target of rapamycin (mTOR) by rapamycin in a murine model of lipopolysaccharide-induced acute lung injury.

BACKGROUND: The mammalian target of rapamycin (mTOR) pathway, a key cellular signaling pathway associated with various cellular functions, has distinct roles in the inflammatory process. In this study, the mTOR inhibitor rapamycin (Rapa) was used to test whether inhibition of mTOR activation attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a murine model. METHODS: Mice pretreated with Rapa or vehicle were given LPS intratracheally. Local cell numbers and inflammatory cytokines present in the bronchoalveolar lavage fluid (BAL), wet-to-dry weight ratio, histopathology of the lungs, and survival were evaluated. RESULTS: The phosphorylation of S6, a major downstream target of mTOR, had a 3-fold increase in lung tissue after LPS stimulation, but the increase was blocked by Rapa. Rapa reduced the levels of TNF-α (LPS vs. LPS + Rapa, (1672.74 ± 193.73) vs. (539.17 ± 140.48) pg/ml, respectively; P < 0.01) and IL-6 (LPS vs. LPS + Rapa: (7790.88 ± 1170.54) vs. (1968.57 ± 474.62) pg/ml, respectively; P < 0.01) in the BAL fluid. However, Rapa had limited effects on the overall severity of ALI, as determined by the wet-to-dry weight ratio of the lungs, number of neutrophils in the BAL fluid, and changes in histopathology. In addition, Rapa failed to reduce mortality in the LPS-induced ALI model. CONCLUSIONS: We confirmed that mTOR was activated during LPS-induced ALI and strongly inhibited by Rapa. Although Rapa reduced the levels of the mediators of inflammation, the overall severity and survival of the ALI murine model were unchanged.

Analysis of photonic Doppler velocimetry data based on the continuous wavelet transform.

The short time Fourier transform (STFT) cannot resolve rapid velocity changes in most photonic Doppler velocimetry (PDV) data. A practical analysis method based on the continuous wavelet transform (CWT) was presented to overcome this difficulty. The adaptability of the wavelet family predicates that the continuous wavelet transform uses an adaptive time window to estimate the instantaneous frequency of signals. The local frequencies of signal are accurately determined by finding the ridge in the spectrogram of the CWT and then are converted to target velocity according to the Doppler effects. A performance comparison between the CWT and STFT is demonstrated by a plate-impact experiment data. The results illustrate that the new method is automatic and adequate for analysis of PDV data.

[Infection of human papillomavirus 16/18 DNA in patients with head and neck squamous cell carcinoma and its relationship with expression of Ki-67 and P53 protein].

OBJECTIVE: To detect the infection of human papillomavirus (HPV) 16/18 in patients with head and neck squamous cell carcinoma and explore the relationship between HPV infection and expressions of Ki-67 and P53 proteins in tumor tissue. METHOD: The level of HPV 16/18 DNA was measured by real time polymerase chain reaction, and Ki-67 and P53 proteins were measured by immunohistochemistry in tissues from head and neck squamous cell carcinoma. RESULTS: HPV 16/18 DNA was detected in 62.8% of our patients. In each cancer tissue sample, Ki-67 protein was expressed between 2% to 70%. P53 protein was expressed in 46.15% of our patients. No significant relation was found between HPV 16/18 DNA level and sex, smoking, drinking, and tumor clinical stages. However, level of HPV 16/18 DNA was found to have positive relation with tumor pathological grades and negative relation with P53 protein expression. No relation with Ki-67 protein expression was found. CONCLUSION: Head and neck squamous cell carcinoma may be initiated by HPV 16/18 infection and the mechanism in carcinogenesis involves abnormal expression in P53 protein.

[Lymph node image with ultrasmall superparamagnetic iron oxide and comparison with pathological result].

OBJECTIVE: To assess the characteristics of enhanced magnetic resonance image with ultrasmall superparamagnetic iron oxide (USPIO) in the inflammatory and tumor metastatic rabbit model, and explore its relevance with histologic ultrastructural findings. METHODS: Totally 36 New Zealand white rabbits were randomly divided into lymphadenitis group and metastatic group. Complete Freund's adjuvant was injected into the bilateral dorsal footpads of 18 rabbits to set up ipsilateral lymphadenitis model. The other 18 rabbits received a subcutaneous implantation of VX2 tumor cell suspension (1.5 x 10(7) cells/ml) in both thighs to set up metastatic lymph node model. Magnetic resonance scan were performed 24 hours before and after USPIO (90 micromol Fe/kg) injection. T2 values of each lymph node were measured and lymph node T2 enhancement rate was calculated as well. HE staining, Prussian blue staining, and electronic microscopy were performed to observe the pathological microstructure changes and the distribution of the iron particle in lymph node. Relationship between lymph nodes USPIO enhancement and its microstructures were further analyzed. Results Thirty-six lymph nodes in lymphadenitis group showed different degrees of reactive hyperplasia. Twenty-six lymph nodes in metastatic group were invaded by tumor cell. Non-enhanced scan showed mild difference between T2 signal intensity of the two pathological lymph node types. After USPIO enhancement, inflammatory lymph nodes showed distinct T2 signal reduction at the center, and metastatic lymph nodes showed homogenous and faint T2 signal reduction. Enhancement rate of benign and malignant lymph nodes were 57.39% and 29.45% respectively (P < 0.01). HE staining and Prussian blue staining indicated USPIO particles located mainly in the macrophages at inflammatory lymphatic medulla, while paracortical area and cortical area contained relatively much less USPIO particles due to less macrophages distribution. MRI findings were correlated with the pathological results. Electronic microscopy also verified that the majority of USPIO particles were located in the numerous cytophagic bubbles of macrophages. Lymph nodes metastasis including 4 lymph nodes with completed structure destruction due to entire tumor infiltration, 19 lymph nodes with partially lymph node structure destruction but reduced USPIO-contained macrophage numbers or reduced USPIO particles in macrophages, and 3 lymph nodes with only localized foci tumor metastasis at subcapsular area. Conclusions USPIO enhancement pattern of different lymph nodes is closely related to distribution and functional status of the intra-node macrophages. It may affect the accuracy of the lymph node property diagnosis based on USPIO enhanced image.

Hepatosplenic gammadelta T-cell lymphoma.

AIM: To investigate the clinicopathologic characteristics, immunophenotype and TCR gene rearrangements of hepatosplenic T-cell lymphoma in eight Chinese patients. METHODS: Eight Chinese patients with hepatosplenic gammadelta T-cell lymphomas were studied. Hematoxylin-eosin-stained slides and clinical histories were reviewed. We also carried out immunohistochemical staining for CD3, CD4, CD8, CD20, CD43, CD56, CD79a, UCHL-1, and TCR gammadelta. Rearrangements of TCR gamma and delta chain genes were also studied. RESULTS: The spleens were enlarged and the cut surfaces were homogeneous and red-purple in color without identifiable gross lesions or enlarged hilar lymph nodes. Histologically, lymphoma cells infiltrated the cords of Billroth and often packed the sinuses. Liver biopsy showed lymphoma cell infiltrations in the sinusoids, and three cases showed involvements of the portal tracts. Immunohistochemically lymphoma cells were positive for CD3, CD43, and CD56 in all cases. Four of eight cases were positive for CD8, and all cases were negative for CD4 (6/6). Monoclonal rearrangements of TCR gamma gene were demonstrated by PCR analysis in five out of the eight cases. TCR delta gene rearrangements were detected in six out of the eight cases, which demonstrated single bands on PAGE gel, and the amplification products in two cases were confirmed by sequencing. CONCLUSION: The clinicopathology of hepatosplenic gammadelta T-cell lymphoma in Chinese patients is similar to what was previously reported except that the splenomegaly is not so massive, and CD8 is positive.

[Immunohistochemical investigation of lungs with severe acute respiratory syndrome].

OBJECTIVE: To investigate the roles of different cells in the pulmonary lesions in the severe acute respiratory syndrome (SARS) patients. METHODS: The monoclonal antibodies of CD8, CD20, CD34, LCA, CD56, CD68, and AE1/AE3 are used to demonstrate the different cells in the lung specimens of SARS patients in order to study the patterns of cell responses in this new disease. Meanwhile the HE stained slides were also carefully studied to compare with the results of immunohistochemical staining. RESULTS: The number of capillaries increased and the capillaries clearly outlined the contour of alveolar wall from beginning to early stage of organization, the number of lymphocytes decreased sharply while the number of macrophage remarkably increased, together with proliferation of type II pneumocytes. The numbers of blood vessels decreased in the fibrotic and consolidated lung tissue, and the vessel cavities enlarged, losing the normal contour of alveolar septa. CONCLUSIONS: The lesions in the lung from SARS patients are consisted of the tissue reaction to the inflammatory injury, including extensive exudation, capillary proliferation, fibrosis, and obvious infiltration of macrophages which may play a key role in the pathogenesis of pulmonary lesions of SARS.

[Lung pathology of severe acute respiratory syndrome].

OBJECTIVE: To study the morphological features of the lungs obtained from autopsies of severe acute respiratory syndrome (SARS) patients. METHODS: Bilateral lungs from 7 patients died from SARS were carefully studied grossly and microscopically. All tissues from these cases were routinely processed and carefully studied. RESULTS: All lungs from these cases were extremely expanded and became solid. Microscopically, the edema and fibrin exudates in the alveoli was the most common findings, especially in the early phase of the disease. The hyaline membrane was almost always present in the lungs of these cases. The organization of intra-alveolar fibrin exudates along with the interstitial fibrosis led to obliteration of alveoli and consolidation of lungs. The desquamation and hyperplasia of alveolar lining cells was also apparent. Foci of haemorrhage and lobular pneumonia, even diffuse fungal infection were frequently seen in these specimens. Micro-thrombus were easily found in these lungs. CONCLUSIONS: The lung of SARS from autopsy is characterized by edema, intra-alveolar fibrin exudates, hyaline membrane formation, organization of intra-alveolar exudates and fibrosis, which lead to the obliteration of alveoli and consolidation of lungs.

[Morphological study of severe acute respiratory syndrome (SARS)].

OBJECTIVE: Seven cases of autopsy from SARS patients are studied to investigate the pathogenesis and the pathologic changes of the major organs. METHODS: Detailed gross and microscopic examination of the autopsy specimen is performed, including lung, heart, liver, kidney, spleen and lymph nodes. RESULTS: All of the lungs are markedly enlarged and consolidated. Microscopically, pulmonary edema is a prominent finding, especially at the early stage of the disease (5 days after the onset). The alveolar spaces are filled with fibrinous exudates and lined with hyaline membrane. In 5 cases that undergo over 3 weeks of the course, the main pattern is organization of intra-alveolar deposit, along with fibroblastic proliferation in the alveolar septa, which leads to obliteration of alveolar space and pulmonary fibrosis. All of the lungs show bronchopneumonia, scattered hemorrhage, and proliferation of alveolar epithelial cells with desquamation. Microthrombi are seen in 6 cases. Fungal infection is noted in 2 cases. One of them is disseminative, involving bilateral lungs, heart, and kidney; the other one is diagnosed in hilar lymph nodes. In immune system, hilar and abdominal lymph nodes are usually congested and hemorrhagic, with depletion of lymphocytes, and accompanied with subcapsular sinus histiocytosis. One of the cases shows enlargement of abdominal lymph nodes, which have reduced number of germinal centers. Spleen exhibits atrophy of white pulps, and even lost of white pulps in some areas. The red pulp is markedly congested and hemorrhagic. In 5 cases, cardiomegale is prominent. Thrombosis (2 cases), focal myocarditis (1 case), and fungal myocarditis (1 case) are observed. In addition, liver shows massive necrosis (1 case) and nodular cirrhosis (1 case). CONCLUSIONS: Lung is the major organ affected by SARS, demonstrated as diffuse alveolar damage. It is postulated that viral infection induces severe damage of alveolar epithelial and capillary endothelial cells, leads to pulmonary edema, intra-alveolar fibrin deposit, and hyaline membrane formation. Consequently, intra-alveolar organization and alveolar septal fibrosis causes loss of alveolar spaces, eventually, pulmonary fibrosis and atelectasis. The immune system is often affected, and presented as depletion of lymphoid tissue in lymph nodes and spleen. Secondary infection is a common complication, which should be paid close attention in the management of SARS patients.