Improvement of spatial resolution in photoacoustic microscopy using transmissive adaptive optics with a low-frequency ultrasound transducer.

Maintaining a high spatial resolution in photoacoustic microscopy (PAM) of deep tissues is difficult due to large aberration in an objective lens with high numerical aperture and photoacoustic wave attenuation. To address the issue, we integrate transmission-type adaptive optics (AO) in high-resolution PAM with a low-frequency ultrasound transducer (UT), which increases the photoacoustic wave detection efficiency. AO improves lateral resolution and depth discrimination in PAM, even for low-frequency ultrasound waves by focusing a beam spot in deep tissues. Using the proposed PAM, we increased the lateral resolution and depth discrimination for blood vessels in mouse ears.

Optical coherence tomography with a 2.8-mm beam diameter and sensorless defocus and astigmatism correction.

An optical coherence tomography (OCT) system with a 2.8-mm beam diameter is presented. Sensorless defocus correction can be performed with a Badal optometer and astigmatism correction with a liquid crystal device. OCT B-scans were used in an image-based optimization algorithm for aberration correction. Defocus can be corrected from ? 4.3 ?? D to + 4.3 ?? D and vertical and oblique astigmatism from ? 2.5 ?? D to + 2.5 ?? D . A contrast gain of 6.9 times was measured after aberration correction. In comparison with a 1.3-mm beam diameter OCT system, this concept achieved a 3.7-dB gain in dynamic range on a model retina. Both systems were used to image the retina of a human subject. As the correction of the liquid crystal device can take more than 60 s, the subject's spectacle prescription was adopted instead. This resulted in a 2.5 times smaller speckle size compared with the standard OCT system. The liquid crystal device for astigmatism correction does not need a high-voltage amplifier and can be operated at 5 V. The correction device is small ( 9 ?? mm × 30 ?? mm × 38 ?? mm ) and can easily be implemented in existing designs for OCT.

Transmissive liquid-crystal device for correcting primary coma aberration and astigmatism in biospecimen in two-photon excitation laser scanning microscopy.

All aberrations produced inside a biospecimen can degrade the quality of a three-dimensional image in two-photon excitation laser scanning microscopy. Previously, we developed a transmissive liquid-crystal device to correct spherical aberrations that improved the image quality of a fixed-mouse-brain slice treated with an optical clearing reagent. In this study, we developed a transmissive device that corrects primary coma aberration and astigmatism. The motivation for this study is that asymmetric aberration can be induced by the shape of a biospecimen and/or by a complicated refractive-index distribution in a sample; this can considerably degrade optical performance even near the sample surface. The device's performance was evaluated by observing fluorescence beads. The device was inserted between the objective lens and microscope revolver and succeeded in improving the spatial resolution and fluorescence signal of a bead image that was originally degraded by asymmetric aberration. Finally, we implemented the device for observing a fixed whole mouse brain with a sloping surface shape and complicated internal refractive-index distribution. The correction with the device improved the spatial resolution and increased the fluorescence signal by ?2.4×. The device can provide a simple approach to acquiring higher-quality images of biospecimens.

A systematic framework to derive N-glycan biosynthesis process and the automated construction of glycosylation networks.

BACKGROUND: Abnormalities in glycan biosynthesis have been conclusively related to various diseases, whereas the complexity of the glycosylation process has impeded the quantitative analysis of biochemical experimental data for the identification of glycoforms contributing to disease. To overcome this limitation, the automatic construction of glycosylation reaction networks in silico is a critical step. RESULTS: In this paper, a framework K2014 is developed to automatically construct N-glycosylation networks in MATLAB with the involvement of the 27 most-known enzyme reaction rules of 22 enzymes, as an extension of previous model KB2005. A toolbox named Glycosylation Network Analysis Toolbox (GNAT) is applied to define network properties systematically, including linkages, stereochemical specificity and reaction conditions of enzymes. Our network shows a strong ability to predict a wider range of glycans produced by the enzymes encountered in the Golgi Apparatus in human cell expression systems. CONCLUSIONS: Our results demonstrate a better understanding of the underlying glycosylation process and the potential of systems glycobiology tools for analyzing conventional biochemical or mass spectrometry-based experimental data quantitatively in a more realistic and practical way.

Giant cell tumor of the tendon sheath arising from a membrane surrounding the posterior arch of C1: a case report.

BACKGROUND CONTEXT: Giant cell tumor of the tendon sheath (GCTTS) is a common, benign lesion of the synovial membrane that occurs more often in large joints than in digits. Giant cell tumor of the tendon sheath rarely arises in close proximity to the axial skeleton. PURPOSE: The purpose of the study was to report a rare case of GCTTS arising from the membrane surrounding the posterior arch of the atlas (C1). STUDY DESIGN/SETTING: This is a case report. METHODS: The methods involve clinical findings and review of current literature. RESULTS: In this report, we describe a rare case of GCTTS arising from the membrane surrounding the posterior arch of C1, with no apparent continuity with the facet joint. Here we show the radiographic features, with particular emphasis on positron emission tomography-computerized tomography scans, which have not been previously reported. CONCLUSIONS: We experienced an extremely rare case of GCTTS arising from the membrane surrounding the posterior arch of the C1 vertebra. In spite of the rarity of this disease, GCTTS should be considered in the differential diagnosis of the axial skeletal lesion. Awareness of GCTTS is important because its radiographic features may simulate other neoplastic lesions in the spine.

Performance of a q-plate tunable retarder in reflection for the switchable generation of both first- and second-order vector beams.

We examine the performance of a tunable liquid crystal q-plate in a reflective geometry. When the device is tuned to a half-wave retardance, it operates as a q-plate with twice the value (2q) by adding a quarter-wave retarder between the mirror and the q-plate. However, when the device is tuned to a quarter-wave retardance, it acts as the original q-plate without the retarder. Experimental results are shown. Using an input tunable polarization state generator, the system allows the switchable production of all states on both the first- and second-order Poincaré spheres.

New Magnetic Resonance Imaging Features Predictive for Post-Treatment Ambulatory Function: Imaging Analysis of Metastatic Spinal Cord Compression.

STUDY DESIGN: This is a retrospective, single-institute, radiographical study. OBJECTIVE: The study aimed to determine the correlation of magnetic resonance imaging (MRI) findings observed in metastatic spinal cord compression (MSCC) with post-treatment ambulatory status. SUMMARY OF BACKGROUND DATA: Previous studies have reported various predictors of ambulatory outcome in patients with MSCC, but the relationship between the MRI features and post-treatment ambulatory function remains to be elucidated. METHODS: Fifty-six hospitalized patients with MSCC and risk of MSCC were examined using MRI before therapeutic intervention. Circumferential ratio of cord compression (CRCC), clock position of compression, cross-sectional area (CSA), and change in signal intensity of the spinal cord were recorded. Each imaging feature was analyzed statistically regarding unassisted ambulatory status at the time of hospital discharge as the endpoint. RESULTS: CRCC showed a prognostic value for post-treatment ambulatory function. More than half of CRCC predicted poor functional prognosis with statistical significance. However, the site of cord compression expressed by clock position on axial plane showed no relationship with functional prognosis. CSA of the spinal cord was enlarged in 23% of patients at the level of MSCC, which indicated that cord compression could also be formed by a relative relationship between cord swelling and surrounding mass effect. The said patients showed a better functional outcome. High intensity of the spinal cord on T2-weighted sagittal image was not useful because of lack of inter-rater reliability. CONCLUSION: CRCC on axial T2 image can guide clinicians to identify cancer patients at risk of paraplegia because of MSCC. More than half of CRCC entails urgent treatment despite preserved ambulatory function. Furthermore, some cases of MSCC accompany increased cord CSA. The measurement is also a useful guide to balance the risk and benefit of systemic steroid therapy. MRI is the key imaging modality in the risk assessment of MSCC. LEVEL OF EVIDENCE: 4.

Analysis of a segmented q-plate tunable retarder for the generation of first-order vector beams.

In this work we study a prototype q-plate segmented tunable liquid crystal retarder device. It shows a large modulation range (5π rad for a wavelength of 633 nm and near 2π for 1550 nm) and a large clear aperture of one inch diameter. We analyze the operation of the q-plate in terms of Jones matrices and provide different matrix decompositions useful for its analysis, including the polarization transformations, the effect of the tunable phase shift, and the effect of quantization levels (the device is segmented in 12 angular sectors). We also show a very simple and robust optical system capable of generating all polarization states on the first-order Poincaré sphere. An optical polarization rotator and a linear retarder are used in a geometry that allows the generation of all states in the zero-order Poincaré sphere simply by tuning two retardance parameters. We then use this system with the q-plate device to directly map an input arbitrary state of polarization to a corresponding first-order vectorial beam. This optical system would be more practical for high speed and programmable generation of vector beams than other systems reported so far. Experimental results are presented.

Elevation of urinary liver-type fatty acid binding protein after cardiac catheterization related to cardiovascular events.

PURPOSE: Contrast medium (CM) induces tubular hypoxia via endothelial damage due to direct cytotoxicity or viscosity. Urinary liver-type fatty acid binding protein (L-FABP) increases along with tubular hypoxia and may be a detector of systemic circulation injury. The aim of this study was to evaluate the clinical usefulness of detecting increases in urinary L-FABP levels due to administration of CM, as a prognostic biomarker for cardiovascular disease in patients without occurrence of CM-induced nephropathy undergoing cardiac catheterization procedure (CCP). METHODS: Retrospective longitudinal analyses of the relationship between urinary L-FABP levels and occurrence of cardiovascular events were performed (n=29). Urinary L-FABP was measured by ELISA before CCP, and at 6, 12, 24, and 48 hours after CCP. RESULTS: Urinary L-FABP levels were significantly higher at 12 hours (P<0.05) and 24 hours (P<0.005) after CCP compared with before CCP, only in the patients with occurrence of cardiovascular events (n=17), but not in those without cardiovascular events (n=12). The parameter with the largest area under the curve (0.816) for predicting the occurrence of cardiovascular events was the change in urinary L-FABP at 24 hours after CCP. The difference in urinary L-FABP levels (ΔL-FABP ≥11.0 µg/g creatinine) between before CCP and at 24 hours after CCP was a risk factor for the occurrence of cardiovascular events (hazard ratio, 4.93; 95% confidence interval, 1.27-19.13; P=0.021). CONCLUSION: Measurement of urinary L-FABP before CCP and at 24 hours after CCP in patients with mild to moderate renal dysfunction may be an important indicator for risk stratification of onset of cardiovascular events.

Correcting spherical aberrations in a biospecimen using a transmissive liquid crystal device in two-photon excitation laser scanning microscopy.

Two-photon excitation laser scanning microscopy has enabled the visualization of deep regions in a biospecimen. However, refractive-index mismatches in the optical path cause spherical aberrations that degrade spatial resolution and the fluorescence signal, especially during observation at deeper regions. Recently, we developed transmissive liquid-crystal devices for correcting spherical aberration without changing the basic design of the optical path in a conventional laser scanning microscope. In this study, the device was inserted in front of the objective lens and supplied with the appropriate voltage according to the observation depth. First, we evaluated the device by observing fluorescent beads in single- and two-photon excitation laser scanning microscopes. Using a 25× water-immersion objective lens with a numerical aperture of 1.1 and a sample with a refractive index of 1.38, the device recovered the spatial resolution and the fluorescence signal degraded within a depth of 0.6 mm. Finally, we implemented the device for observation of a mouse brain slice in a two-photon excitation laser scanning microscope. An optical clearing reagent with a refractive index of 1.42 rendered the fixed mouse brain transparent. The device improved the spatial resolution and the yellow fluorescent protein signal within a depth of 0-0.54 mm.

Two-photon excitation STED microscopy by utilizing transmissive liquid crystal devices.

Transmissive liquid crystal devices (tLCDs) enable the modification of optical properties, such as phase, polarization, and laser light intensity, over a wide wavelength region at a high conversion efficiency. By utilizing tLCDs, we developed a new two-photon excitation stimulated emission depletion microscopy technique based on a conventional two-photon microscope. Spatial resolution was improved by compensating for phase shifts distributed in the optical path. Using this technique, we observed the fine structures of microtubule networks in fixed biological cells.

Percutaneous sclerotherapy for venous malformations in the extremities: clinical outcomes and predictors of patient satisfaction.

The purpose of this study is to retrospectively evaluate the clinical outcomes and to identify the predictors ofpatient satisfaction after percutaneous sclerotherapy for venous malformations (VMs) in the extremities. A totalof 48 patients with VMs in the extremities over 10 years of age underwent sclerotherapy to relieve symptoms, such as pain, swelling, functional limitations, and cosmetic problems. Self-assessment questionnaires were sentto rate the degree of symptom improvement and level of satisfaction. Clinical and imaging data from medicalrecords were analyzed to obtain information about VMs and sclerotherapy. The predictors for patientsatisfaction were determined by univariate and multivariate analysis of clinical variables. Forty patients (meanage, 28.2 years; range, 11-69 years) responded to the survey. Sixteen patients had VMs in the upper extremities, and 24 patients had VMs in the lower extremities. In 12 patients (30%), adjacent bone change was seen. After amean of 2.6 (range 1-10) sclerotherapy sessions, good response to pain, swelling, dysfunction, and cosmeticproblems was obtained in 83%, 74%, 79%, and 50% of patients, respectively. Thirty-two patients (80%) weresatisfied with their outcomes. On univariate analysis, absence of adjacent bone change, maximum diameter (<6.7 cm), and number of sclerotherapy sessions (<3) were significantly associated with patient satisfaction.Multivariate analysis revealed absence of adjacent bone change (odds ratio, 7.56; 95% confidence interval, 1.02-55.8) as an independent predictor for satisfaction. Thus, adjacent bone change significantly portended adissatisfied patient. In conclusion, percutaneous sclerotherapy was effective to relieve symptoms of VMs in theextremities, and most patients were satisfied with the outcomes. However, adjacent bone change was asignificant predictor of patient dissatisfaction.

Malignant phosphaturic mesenchymal tumor of the pelvis: A report of two cases.

Tumor-induced osteomalacia (TIO) is a rare acquired form of hypophosphatemia commonly associated with phosphaturic mesenchymal tumors (PMTs) located in the bone or soft tissue. Resection of the tumor can cure osteomalacia. Fibroblast growth factor 23 has been identified as a major pathophysiological factor responsible for phosphaturia. The majority of PMTs are benign, and malignant PMTs are uncommon. Even in rare cases, the malignant transformation of PMTs is extremely uncommon. The current study presents two cases in which the patients succumbed to malignant PMTs that developed in the pelvis. The first patient was a 35-year-old female with a malignant PMT occurring as a synchronous double cancer associated with papillary thyroid carcinoma. Diagnosis was difficult, as the multiple uptake on positron emission tomography with 18F-fluorodeoxyglucose presented as pseudofractures mimicking the metastases of thyroid carcinoma. The patient succumbed to rapidly progressive lung metastases. The second patient presented with a pelvic tumor that had developed over 26 years. The patient was diagnosed with a benign PMT by open biopsy and a complete resection was performed. However, two years later, the tumor recurred and lung metastases were observed. The patient ultimately succumbed to respiratory failure due to relapsing lung metastases and disseminated intravascular coagulation. These two cases demonstrate the potential lethality of malignant PMTs and the malignant transformation of benign PMTs. Therefore, TIO patients must be followed up even if diagnosed with a benign tumor. Although TIO is an extremely rare disease, the possibility of malignant PMTs must be recognized.

Radiofrequency ablation for treatment for osteoid osteoma of the scapula using a new three-dimensional fluoroscopic navigation system.

Osteoid osteoma is a relatively common benign skeletal tumor. The traditional standard treatment has been surgical resection of the nidus. Recently, computed tomography (CT)-guided radiofrequency ablation (RFA) has gained favor as a more precise alternative due to potentially less bone destruction. However, CT-guided RFA is limited in treatment for osteoid osteoma involving complex anatomic structures such as cervical spine, pelvis, or scapula because of difficulty in approach and proximity to neurovascular structures. To solve this problem, we investigated RFA using a new real-time three-dimensional fluoroscopic navigation system. We report its technical procedure and use in a rare case of osteoid osteoma of the scapula.

Transarterial embolization (TAE) of sacral giant cell Tumor (GCT) using spherical parmanent embolic material superabsorbant polymer microsphere (SAP-MS).

PURPOSE: We retrospectively evaluated our experience of transcatheter arterial embolization (TAE) of the sacral GCT with use of a spherical permanent embolic agent, superabsorbant polymer microsphere (SAP-MS) as an alternative treatment modality. MATERIALS AND METHODS: From 1997 to 2011, four patients with sacral GCT were treated with TAE. In all cases, SAP-MS was used as an embolic material. The effects of TAE were evaluated for improvement of patients' symptoms, radiographic change such as vascularity of tumor, size of tumor and occurrence of reossification. RESULTS: Of the four patients, three responded favorably to TAE with improvement in pain and neurologic symptoms with long-term follow up. Diminished vascularity, stabilization of tumor size and reossification were shown radiographically. One patient died because of tumor growth 26 months after the initial TAE. CONCLUSION: In sacral GCT, TAE using SAP-MS might be useful for symptom improvement, reossification of the lesion and stabilization of tumor size.

In-line FINCH super resolution digital holographic fluorescence microscopy using a high efficiency transmission liquid crystal GRIN lens.

We report a new optical arrangement that creates high-efficiency, high-quality Fresnel incoherent correlation holography (FINCH) holograms using polarization sensitive transmission liquid crystal gradient index (TLCGRIN) diffractive lenses. In contrast, current universal practice in the field employs a reflective spatial light modulator (SLM) to separate sample and reference beams. Polarization sensitive TLCGRIN lenses enable a straight optical path, have >90% transmission efficiency, are not pixilated, and are free of many limitations of reflective SLM devices. For each sample point, two spherical beams created by a glass lens in combination with a polarization sensitive TLCGRIN lens interfere and create a hologram and resultant super resolution image.

Functional analysis of cases of tumor endoprostheses with deep infection around the knee: a multi institutional study by the Japanese Musculoskeletal Oncology Group (JMOG).

BACKGROUND: Although intensive studies have been conducted to clarify the incidence, risks, and management methods of deep infection of tumor endoprostheses, limited data have been published in respect of the impact of such deep infection on the function of the corresponding limb. METHODS: Clinical data of 125 patients (infection group 57, control group 68) with malignant bone and soft tissue tumors around the knee enrolled with the Japanese Musculoskeletal Oncology Group were collected. We analyzed the impact of deep infection of tumor endoprostheses on the limb salvage status together with that on the function of the salvaged limb. The definition of deep infection was based on the recommendations of the Centers for Disease Control and Prevention. The functional evaluation was based on the functional classification system established by the International Society of Limb Salvage and the Musculoskeletal Tumor Society. RESULTS: Infection together with extracapsular resection was demonstrated to be a risk factor for late amputation. There were no significant differences in the functional scores for "pain," "support," "walking," or "gait" between the infection and control groups. The risk factors identified for a loss of score for "functional activities" were deep infection, age, duration of operation, and extracapsular resection. The infection group also showed a significant lower score loss in "emotion". As for the overall functional scores, the risk factors identified for lower scores were deep infection and age. The mean scores for the infection group and control group were 19.3 (64.3 %) and 21.6 (72 %), respectively. Although the difference was confirmed to be statistically significant, the actual difference was only 2.3 (10.6 % reduction). CONCLUSIONS: Infection was a major risk factor for late amputation. Limbs salvaged by management of deep infection may show loss of function; however, the impact may be limited.

Whole-body MR imaging in detecting phosphaturic mesenchymal tumor (PMT) in tumor-induced hypophosphatemic osteomalacia.

We present 2 cases of tumor-induced osteomalacia (TIO). Both patients had histories of long-term bone and muscle pain. Laboratory data revealed hypophosphatemia. Whole-body magnetic resonance (MR) imaging (WB-MRI) clearly depicted a small subcutaneous mass in the left thigh of the first patient and a right acetabular mass in the second patient. These lesions were pathologically proven to be hemangiopericytoma-phosphaturic mesenchymal tumors (PMT).

Neoadjuvant and adjuvant chemotherapy with high-dose ifosfamide, doxorubicin, cisplatin and high-dose methotrexate in non-metastatic osteosarcoma of the extremities: a phase II trial in Japan.

From 1997 to 2003, 40 patients (all <40 years of age) with non-metastatic osteosarcoma of the extremities were treated with OOS-D and definitive surgery. Two cycles of doxorubicin 90 mg/m(2) plus cisplatin 120 mg/m(2) and ifosfamide 15 g/m(2) were given as neoadjuvant chemotherapy, and two cycles of doxorubicin/cisplatin and ifosfamide, and two cycles of high-dose methotrexate (10-12 g/m(2)) were given post-operatively. All patients underwent limb salvage surgeries, and 66% showed good response to neoadjuvant chemotherapy. With a median follow-up period of 117 months, 31 of the evaluable 40 patients were continuously disease-free, 7 were currently alive with no evidence of disease, and 2 died of disease. There was no local recurrence. The 5-year event-free and overall survival rates were 83 and 98%, respectively. The 10-year event-free and overall survival rates were 80 and 95%, respectively. The major form of toxicity was haematological one.

Deep infection in tumor endoprosthesis around the knee: a multi-institutional study by the Japanese musculoskeletal oncology group.

BACKGROUND: The incidence of endoprosthesis failure has been well studied, but few studies have described the clinical characteristics of deep infection in tumor prostheses. This study aimed to analyze the characteristics of deep infection in tumor endoprostheses around the knee. METHODS: We analyzed clinical data of 57 patients with deep infections involving tumor endoprostheses around the knee enrolled from the Japanese Musculoskeletal Oncology Group. Profile of clinical presentation including time between surgery and infection, initial symptoms/blood tests and microbial cultures was evaluated. In addition pre-, intra-, and postoperative clinical factors influencing clinical presentation and treatment outcomes of infections were analyzed. RESULTS: Mean interval between the initial operation and diagnosis was 13 months, and mean time required for infection control was 12 months. The most common pathogen was Staphylococcus. Infection control rates were significantly higher when prostheses were removed rather than salvaged. Ten-year prosthesis survival and limb salvage rates were 41.6% and 75.6%, respectively. Analysis of underlying clinical factors suggested that soft-tissue condition significantly influenced the duration of the infection control period and likelihood of limb salvage. CONCLUSIONS: Infection control is a prolonged process. Deep infection frequently results in amputation or prosthesis loss. Intensive analysis of clinical characteristics may aid infection control.