MDISCO: A High-Throughput Tissue-Clearing Protocol for Preservation of Endogenous Fluorescence in Whole Mouse Brains.

Three dimensional morphometry of the knee to design the total knee arthroplasty for Chinese population

We aimed to retrospectively investigate the morphology of the resected surfaces of femurs in Chinese patients who underwent total knee arthroplasty (TKA) and to assess the suitability of contemporary femoral components. Measurements on three-dimensional reconstruction after virtual bone cutting were performed on 142 knees from Chinese TKA candidates. The anteroposterior (AP) and mediolateral (ML) dimensions, aspect ratio (ML/AP), and posterior condylar angle (PCA) were measured in the axial plane; the height and length of medial and lateral anterior condyles and the maximal width of the anterior condyles were measured in the frontal plane. Femurs were matched to the prosthesis with the closest AP size. The ML dimensions of femurs were compared with the ML dimensions of the prosthesis. The AP and ML dimensions were significantly larger in male knees (p < 0.01), whereas the difference of aspect ratios was not found to be significantly different between genders (p = 0.26). Both medial and lateral heights of the anterior condyles were significantly higher in men after normalization by AP (p < 0.01 and p < 0.05, respectively). The mean PCA averaged 3.8 degrees for Chinese subjects. The overall prevalence of clinically significant overhang was 6.4% in males and 4.8% in females. The design of femoral prosthesis with alternative ML dimensions of the femoral component is a solution to sufficiently avoid overhang while retaining ideal coverage when dealing with a high variation. Chinese men had higher anterior condyles than women after normalization by AP dimension. The mean PCA was 3.8 degrees for all patients with high variability.

This study analyzed morphological differences in the resected proximal tibial surfaces of Chinese males and females undergoing total knee arthroplasty (TKA) and compared the measurements with the dimensions of five currently used tibial implants. The mediolateral (ML), middle anteroposterior (AP), medial anteroposterior (MAP), and lateral anteroposterior (LAP) dimensions of the resected tibial surfaces of 976 Chinese TKA knees (177 male, 799 female) were measured. The ML/AP ratio of every knee was calculated. These morphological data were compared with the dimensions of five currently used tibial implants. The ML, AP, MAP, and LAP dimensions of the resected proximal tibias showed significant differences according to gender. Compared with currently used tibial implants, the smaller implants showed tibial ML undersizing and the larger implants showed tibial ML overhang. The ML/AP aspect ratio progressively decreased with increasing AP dimension in the resected proximal tibias, which contrasts with the relatively constant or increased (NexGen) aspect ratio in currently used tibial implants. Males showed a higher ML/AP aspect ratio than females for a given AP dimension. This indicates that for an implant with a given AP dimension, the tibial ML dimension tends to be undersized in males and to overhang in females. The results of this study may provide fundamental data for designing suitable tibial implants for use in the Chinese population, especially for design of gender-specific prostheses. II.

Computed Tomography Morphometric Study of Gender Differences in Osteoarthritis Proximal Tibias

BackgroundMatching tibial component with resected tibia dimensions is essential for good clinical outcomes in total knee arthroplasty.The aim of this study was to determine the sex differences in anthropometry at the surface of the resected proximal tibia in Chinese population and compare the anthropometric values with the dimensions of available tibial components currently used in China.MethodsThe anthropometric characteristics of the proximal tibias in 241 Chinese individuals (121 males, 120 females) were assessed via computed tomography imaging. We measured the mediolateral (ML), anteroposterior (AP), medial and lateral anteroposterior dimensions and the ML/AP aspect ratio of the resected proximal tibial surface. The ML/AP aspect ratios were classified into 3 groups on the basis of the AP dimensions (< 48 mm, 48–51 mm, > 51 mm) to compare sex differences. All the anthropometric data were compared with the dimensions of the six tibial components currently used.ResultsThe tibias ML and AP dimensions of females were significantly smaller than that of males (69.5 ± 3.4 mm, 46.7 ± 2.3 mm vs. 78.4 ± 3.2 mm, 52.6 ± 2.9 mm ). We found females had a smaller ML/AP aspect ratio than males in the subgroups (< 48 mm P = 0.009; 48–51 mm P < 0.001; >51 mm P = 0.043). Compared with component sizes, there was a mismatch between tibial morphology and the dimensions of all the implants. Tibial components with smaller AP measurements were undersized in the ML dimension, and those with larger AP measurements were oversized in the ML dimension in males and females.ConclusionIn the Chinese population, females have smaller dimensions and ML/AP aspect ratios than their male counterparts. The results of this study can provide fundamental data on designing optimal tibial components, especially for design of sex-specific prostheses with different ML/AP aspect ratios for the Chinese males and females.

Brain functions are performed by highly interconnected neurons distributed across the whole brain. Imaging of the whole brain at subcellular resolution is crucial for precise understanding of the pathological and therapeutic mechanisms of neuropsychiatric disorders; however, microscopic imaging of the whole brain remains a challenge due to the trade-offs between imaging speed and spatial resolution. To overcome this, we have recently developed block-face serial microscopy tomography (FAST), which is a novel serial-section imaging system using high-speed spinning-disk confocal microscopy. FAST enables high-throughput imaging of whole mouse brains (2.4 h per brain at maximum speed) and can be applied to nonhuman primate whole brains and human postmortem brains. Whole-brain neuronal activation mapping using FAST and Arc-dVenus mice reveals differences in brain-wide activation patterns between acute and chronic stress exposure. These applications of FAST are expected to contribute to unbiased and hypothesis-free analyses for understanding the anatomical and functional relationships of the brain underlying disease and pharmacotherapy.

Anthropometry of the Proximal Tibia of Patients With Knee Arthritis in Shanghai

The pectinofoveal fold is an intraarticular structure of the hip that has had only limited study in the clinical and anatomic literature. This fold may resemble a hip plica; however, symptomatic hip plicae are now being recognized and treated at hip arthroscopy. We wished to determine the frequency and appearance of the pectinofoveal fold on hip MR arthrography. By defining the variations in its appearance, the normal pectinofoveal fold can be distinguished from pathologic hip plicae. One hundred fifty-two hip MR arthrography examinations of patients who subsequently underwent hip arthroscopy were retrospectively reviewed. Each MR examination was reviewed for the presence of a pectinofoveal fold. If present, the fold was measured in the anteroposterior, mediolateral, and superior-inferior dimensions; evaluated for smooth or irregular contour; and evaluated for a femoral or capsular site of insertion. The pectinofoveal fold was visualized on hip MR arthrograms in 144 of the 152 (95%) patients and visualized at hip arthroscopy in 150 of the 152 (99%) patients. The average thickness of the fold was 2.6 mm (range, 1-13 mm) in the mediolateral dimension and 17 mm (range, 1-32 mm) in the anteroposterior dimension. The average length of the fold in the superior-inferior dimension was 23.3 mm (range, 7-44 mm). The pectinofoveal fold had a smooth contour in 75 of the 144 (52%) patients with examinations that showed the fold and an irregular contour in 69 of 144 (48%) patients. The fold was found to insert onto the capsule in 108 of 144 (75%) patients and onto the femur in the remaining 36. The pectinofoveal fold should almost always be visualized at MR arthrography. The fold can have various appearances and attachment sites, and these normal variations should not be mistaken for fold abnormalities. These findings should be useful in distinguishing this normal structure from normal and pathologic plicae.

We aimed to retrospectively investigate the morphology of the resected surfaces of femurs in Chinese patients who underwent total knee arthroplasty (TKA) and to assess the suitability of contemporary femoral components. Measurements on three-dimensional reconstruction after virtual bone cutting were performed on 142 knees from Chinese TKA candidates. The anteroposterior (AP) and mediolateral (ML) dimensions, aspect ratio (ML/AP), and posterior condylar angle (PCA) were measured in the axial plane; the height and length of medial and lateral anterior condyles and the maximal width of the anterior condyles were measured in the frontal plane. Femurs were matched to the prosthesis with the closest AP size. The ML dimensions of femurs were compared with the ML dimensions of the prosthesis. The AP and ML dimensions were significantly larger in male knees (p

Whole-brain imaging is important for understanding brain functions through deciphering tissue structures, neuronal circuits, and single-neuron tracing. Thus, many clearing methods have been developed to acquire whole-brain images or images of three-dimensional thick tissues. However, there are several limitations to imaging whole-brain volumes, including long image acquisition times, large volumes of data, and a long post-image process. Based on these limitations, many researchers are unsure about which light microscopy is most suitable for imaging thick tissues. Here, we compared fast-confocal microscopy with light-sheet fluorescence microscopy for whole-brain three-dimensional imaging, which can acquire images the fastest. To compare the two types of microscopies for large-volume imaging, we performed tissue clearing of a whole mouse brain, and changed the sample chamber and low- magnification objective lens and modified the sample holder of a light-sheet fluorescence microscope. We found out that light-sheet fluorescence microscopy using a 2.5× objective lens possesses several advantages, including saving time, large-volume image acquisitions, and high Z-resolution, over fast-confocal microscopy, which uses a 4× objective lens. Therefore, we suggest that light-sheet fluorescence microscopy is suitable for whole mouse brain imaging and for obtaining high-resolution three-dimensional images.

Large volumes imaging with microscopic resolution is limited by light scattering. In the last few years based on refractive index matching, different clearing approaches have been developed. Organic solvents and water-based optical clearing agents have been used for optical clearing of entire mouse brain. Although these methods guarantee high transparency and preservation of the fluorescence, though present other non-negligible limitations. Tissue transformation by CLARITY allows high transparency, whole brain immunolabelling and structural and molecular preservation. This method however requires a highly expensive refractive index matching solution limiting practical applicability. In this work we investigate the effectiveness of a water-soluble clearing agent, the 2,2'-thiodiethanol (TDE) to clear mouse and human brain. TDE does not quench the fluorescence signal, is compatible with immunostaining and does not introduce any deformation at sub-cellular level. The not viscous nature of the TDE make it a suitable agent to perform brain slicing during serial two-photon (STP) tomography. In fact, by improving penetration depth it reduces tissue slicing, decreasing the acquisition time and cutting artefacts. TDE can also be used as a refractive index medium for CLARITY. The potential of this method has been explored by imaging a whole transgenic mouse brain with the light sheet microscope. Moreover we apply this technique also on blocks of dysplastic human brain tissue transformed with CLARITY and labeled with different antibody. This clearing approach significantly expands the application of single and two-photon imaging, providing a new useful method for quantitative morphological analysis of structure in mouse and human brain.

Multiphoton imaging has evolved as an indispensable tool in cell biology and holds prospects for clinical applications. When addressing endogenous signals such as coherent anti-Stokes Raman scattering (CARS) or second harmonic generation, it requires intense laser irradiation that may cause photodamage. We report that increasing endogenous fluorescence signal upon multiphoton imaging constitutes a marker of photodamage. The effect was studied on mouse brain in vivo and ex vivo, on ex vivo human brain tissue samples, as well as on glioblastoma cells in vitro, demonstrating that this phenomenon is common to a variety of different systems, both ex vivo and in vivo. CARS microscopy and vibrational spectroscopy were used to analyze the photodamage. The development of a standard easy-to-use model that employs rehydrated cryosections allowed the characterization of the irradiation-induced fluorescence and related it to nonlinear photodamage. In conclusion, the monitoring of endogenous two-photon excited fluorescence during label-free multiphoton microscopy enables to estimate damage thresholds ex vivo as well as detect photodamage during in vivo experiments.

Comparison of intraoperative anthropometric measurements of the proximal tibia and tibial component in total knee arthroplasty.

Editor's evaluation: Brain atlas for glycoprotein hormone receptors at single-transcript level

Recently, total knee arthroplasty (TKA) designs that allow the use of narrow-version femoral implants have been introduced to avoid femoral overhang. The purpose of this study was to investigate the frequency of the use of narrow-version femoral implants and identify the difference in radiographic parameters between using a narrow-version femoral implant and a standard-version femoral implant in TKA. A retrospective study was conducted on 504 primary TKAs using a TKA system (Anthem or Persona) that allowed narrow-version femoral implants. Anteroposterior (AP) dimension, mediolateral (ML) dimension, and modified aspect percentage ratio (ML/AP dimension) of the distal femur in preoperative radiographs were compared between a standard-version group (n = 275) and a narrow-version group (n = 229). A cut-off value of a modified aspect percentage ratio indicating the need for a narrow-version femoral implant was determined using the receiver operating characteristic (ROC) curve. Mean ML dimension was 80.9 ± 6.1mm in the standard-version group and 77.3 ± 4.4mm in the narrow-version group (p < 0.001). Mean modified aspect percentage ratio was 138.8 ± 8.1% in the standard-version group and 131.7 ± 6.3% in the narrow-version group (p < 0.001). The optimum cut-off point of the modified aspect percentage ratio for narrow-version femoral implants was 135.4% (sensitivity: 72.0%; specificity: 66.7%) for Anthem and 133.3% (sensitivity: 75.9%, specificity: 76.4%) for Persona. In the narrow-version femoral implant group, the ML dimension and the mean modified aspect percentage ratio were smaller than in the standard-version femoral implant group. A smaller modified aspect percentage ratio of the distal femur in preoperative radiographs could predict the need for narrow-version femoral implants in TKA. It was suggested that the cut-off point could be suggested as 135.4% for Anthem TKA design and 133.3% for Persona TKA design. These radiographic parameters are cost-effective and easily applicable for planning a TKA.A smaller modified aspect percentage ratio of the distal femur in preoperative radiographs could predict the need for narrow-version femoral implants in TKA. The cut-off point was 135.4% for Anthem TKA design and 133.3% for Persona TKA design.