Analysis of 3D pathology samples using weakly supervised AI.

Human tissue, which is inherently three-dimensional (3D), is traditionally examined through standard-of-care histopathology as limited two-dimensional (2D) cross-sections that can insufficiently represent the tissue due to sampling bias. To holistically characterize histomorphology, 3D imaging modalities have been developed, but clinical translation is hampered by complex manual evaluation and lack of computational platforms to distill clinical insights from large, high-resolution datasets. We present TriPath, a deep-learning platform for processing tissue volumes and efficiently predicting clinical outcomes based on 3D morphological features. Recurrence risk-stratification models were trained on prostate cancer specimens imaged with open-top light-sheet microscopy or microcomputed tomography. By comprehensively capturing 3D morphologies, 3D volume-based prognostication achieves superior performance to traditional 2D slice-based approaches, including clinical/histopathological baselines from six certified genitourinary pathologists. Incorporating greater tissue volume improves prognostic performance and mitigates risk prediction variability from sampling bias, further emphasizing the value of capturing larger extents of heterogeneous morphology.

Chondrosarcoma evaluation using hematein-based x-ray staining and high-resolution 3D micro-CT: a feasibility study.

BACKGROUND: Chondrosarcomas are rare malignant bone tumors diagnosed by analyzing radiological images and histology of tissue biopsies and evaluating features such as matrix calcification, cortical destruction, trabecular penetration, and tumor cell entrapment. METHODS: We retrospectively analyzed 16 cartilaginous tumor tissue samples from three patients (51-, 54-, and 70-year-old) diagnosed with a dedifferentiated chondrosarcoma at the femur, a moderately differentiated chondrosarcoma in the pelvis, and a predominantly moderately differentiated chondrosarcoma at the scapula, respectively. We combined a hematein-based x-ray staining with high-resolution three-dimensional (3D) microscopic x-ray computed tomography (micro-CT) for nondestructive 3D tumor assessment and tumor margin evaluation. RESULTS: We detected trabecular entrapment on 3D micro-CT images and followed bone destruction throughout the volume. In addition to staining cell nuclei, hematein-based staining also improved the visualization of the tumor matrix, allowing for the distinction between the tumor and the bone marrow cavity. The hematein-based staining did not interfere with further conventional histology. There was a 5.97 ± 7.17% difference between the relative tumor area measured using micro-CT and histopathology (p = 0.806) (Pearson correlation coefficient r = 0.92, p = 0.009). Signal intensity in the tumor matrix (4.85 ± 2.94) was significantly higher in the stained samples compared to the unstained counterparts (1.92 ± 0.11, p = 0.002). CONCLUSIONS: Using nondestructive 3D micro-CT, the simultaneous visualization of radiological and histopathological features is feasible. RELEVANCE STATEMENT: 3D micro-CT data supports modern radiological and histopathological investigations of human bone tumor specimens. It has the potential for being an integrative part of clinical preoperative diagnostics. KEY POINTS: • Matrix calcifications are a relevant diagnostic feature of bone tumors. • Micro-CT detects all clinically diagnostic relevant features of x-ray-stained chondrosarcoma. • Micro-CT has the potential to be an integrative part of clinical diagnostics.

Revealing the complexity of meniscus microvasculature through 3D visualization and analysis.

Three-dimensional information is essential for a proper understanding of the healing potential of the menisci and their overall role in the knee joint. However, to date, the study of meniscal vascularity has relied primarily on two-dimensional imaging techniques. Here we present a method to elucidate the intricate 3D meniscal vascular network, revealing its spatial arrangement, connectivity and density. A polymerizing contrast agent was injected into the femoral artery of human cadaver legs, and the meniscal microvasculature was examined using micro-computed tomography at different levels of detail and resolution. The 3D vascular network was quantitatively assessed in a zone-base analysis using parameters such as diameter, length, tortuosity, and branching patterns. The results of this study revealed distinct vascular patterns within the meniscus, with the highest vascular volume found in the outer perimeniscal zone. Variations in vascular parameters were found between the different circumferential and radial meniscal zones. Moreover, through state-of-the-art 3D visualization using micro-CT, this study highlighted the importance of spatial resolution in accurately characterizing the vascular network. These findings, both from this study and from future research using this technique, improve our understanding of microvascular distribution, which may lead to improved therapeutic strategies.

Multiscale and multimodal imaging for three-dimensional vascular and histomorphological organ structure analysis of the pancreas.

Exocrine and endocrine pancreas are interconnected anatomically and functionally, with vasculature facilitating bidirectional communication. Our understanding of this network remains limited, largely due to two-dimensional histology and missing combination with three-dimensional imaging. In this study, a multiscale 3D-imaging process was used to analyze a porcine pancreas. Clinical computed tomography, digital volume tomography, micro-computed tomography and Synchrotron-based propagation-based imaging were applied consecutively. Fields of view correlated inversely with attainable resolution from a whole organism level down to capillary structures with a voxel edge length of 2.0 µm. Segmented vascular networks from 3D-imaging data were correlated with tissue sections stained by immunohistochemistry and revealed highly vascularized regions to be intra-islet capillaries of islets of Langerhans. Generated 3D-datasets allowed for three-dimensional qualitative and quantitative organ and vessel structure analysis. Beyond this study, the method shows potential for application across a wide range of patho-morphology analyses and might possibly provide microstructural blueprints for biotissue engineering.

Microhardness Measurements on Tooth and Alveolar Bone in Rodent Oral Disease Models.

The mechanical property, microhardness, is evaluated in dental enamel, dentin, and bone in oral disease models, including dental fluorosis and periodontitis. Micro-CT (µCT) provides 3D imaging information (volume and mineral density) and scanning electron microscopy (SEM) produces microstructure images (enamel prism and bone lacuna-canalicular). Complementarily to structural analysis by µCT and SEM, microhardness is one of the informative parameters to evaluate how structural changes alter mechanical properties. Despite being a useful parameter, studies on microhardness of alveolar bone in oral diseases are limited. To date, divergent microhardness measurement methods have been reported. Since microhardness values vary depending on the sample preparation (polishing and flat surface) and indentation sites, diverse protocols can cause discrepancies among studies. Standardization of the microhardness protocol is essential for consistent and accurate evaluation in oral disease models. In the present study, we demonstrate a standardized protocol for microhardness analysis in tooth and alveolar bone. Specimens used are as follows: for the dental fluorosis model, incisors were collected from mice treated with/without fluoride-containing water for 6 weeks; for ligature-induced periodontal bone resorption (L-PBR) model, alveolar bones with periodontal bone resorption were collected from mice ligated on the maxillary 2nd molar. At 2 weeks after the ligation, the maxilla was collected. Vickers hardness was analyzed in these specimens according to the standardized protocol. The protocol provides detailed materials and methods for resin embedding, serial polishing, and indentation sites for incisors and alveolar. To the best of our knowledge, this is the first standardized microhardness protocol to evaluate the mechanical properties of tooth and alveolar bone in rodent oral disease models.

Does the choice of the measuring technique affect the comparison of fit between zirconia and cobalt-chromium prostheses?

AIMS: The objectives of the study were to compare the adaptation of presintered zirconia and cobalt- chromium prostheses using microcomputed tomography (µCT), scanning electron microscopy (SEM), and stereomicroscope (SM). MATERIALS AND METHODS: Twenty-four fixed dental prostheses (FDPs) were fabricated on metal abutments, duplicated from maxillary first premolar and first molar prepared on a typodont model. Teeth were reduced to obtain chamfer of 1.2 mm and reduction occlusaly of 2 mm occlusal. Scanning of the abutments was done with random assignment to two groups receiving the FDPs made from soft-milled Co-Cr (n = 12) and zirconia (n = 12). Marginal and internal gaps were assessed using three evaluation techniques (X-ray microcomputer tomography, SEM, and stereomicroscopy). STATISTICAL ANALYSIS USED: Comparison of the results was made using Levene and analysis of variance tests (α =0.05). RESULTS: Irrespective of the material tested, statistical differences were found between the measuring techniques (P = 0.001 overall); the obtained mean gaps were for CT scan (92.60 ± 13.31), for SEM (101.92 ± 23.03), and for SM (113.44 ± 14.68): the multiple comparisons between techniques found a significant difference between CT and SM (P < 0.001), and SEM and SM (P = 0.025). When materials were compared within each measuring technique, Co-Cr showed lower values compared to zirconia in SEM (P < 0.001) and Stereo (P = 0.049); similar results were found in CT. CONCLUSIONS: Results values differed with the chosen measuring technique. Co-Cr prostheses had a better fit than zirconia prostheses in SEM and Stereo. µCT showed comparable results to SEM, smaller than SM results.

Microcomputed tomography analysis of curved root canal preparation when coronal flaring and glide path files used with heat-treated nickel titanium rotary files.

The objective was to evaluate the effect of glide path and coronal flaring on the dentin volume removal and percentage of touched walls in curved canals using two heat-treated rotary files. The mesiobuccal canal of forty-eight, randomly selected, extracted mandibular molars was divided into two groups of 24 each, according to the type of instrument used (RACE EVO and EdgeSequel rotary files). Each group was further divided into three subgroups; Group (A): Control using one file shaped to 04/30, Group (B) with a glide path (EdgeGlidePath (EGP)), and Group (C): with a glide path and coronal flaring (EGP and EdgeTaper Platinum (ETP) SX file respectively). The root canals were then instrumented using the assigned instruments. The assessment was carried out using micro-CT. The comparison of the mean values of the tested groups about dentin volume removal and percentage of untouched walls did not reach statistical significance (p<0.05). Glide path and coronal flaring had an insignificant effect on the dentin volume removal and percentage of untouched walls in curved canals.

Micro-computed tomographic evaluation of the shaping ability of three nickel-titanium rotary systems in the middle mesial canal of mandibular first molars: an ex vivo study based on 3D printed tooth replicas.

BACKGROUND: The preparation of the middle mesial (MM) canal of mandibular molars represents a challenge because it is often curved, narrow, and close to the root concave. The purpose of this study was to evaluate the ex vivo shaping ability of 3 nickel-titanium (NiTi) rotary systems in the MM canal using 3D printed resin tooth replicas. METHODS: A permanent mandibular first molar with a MM canal was acquired from a pool of extracted teeth and reproduced by a 3D printer. The resin tooth replicas (n = 18) were equally assigned to 3 groups for the evaluation of the shaping abilities of 3 NiTi rotary systems (OneShape [OS], Twisted Files [TF], and ProTaper Gold [PTG]) according to the manufacturer's recommendations. The tooth replicas were scanned by micro-computed tomography (micro-CT) twice before and after instrumentation of the mesiobuccal (MB), mesiolingual (ML), and MM root canals. After 3D reconstruction, the canal straightening, change of root canal volume and surface area, the mesial and distal canal wall thickness and canal transportation at the levels of 1, 2, and 3 mm below furcation were assessed. One-way variance analysis and Turkey's post hoc test were used for comparisons of the means among different groups, and paired-t test was used to compare the mesial and distal sides of the mesial roots. RESULTS: As compared with OS and TF, the use of PTG in preparation of MM canals resulted in significantly more straightening of canal curvature (p < 0.05), greater post-instrumentation canal volume and surface area, and thinner mesial and distal remaining canal wall thickness at 1, 2 and 3 mm below furcation (all p < 0.05). Regarding the root canal transportation in the mesiodistal direction, there was no significant difference among the 3 instruments (all p > 0.05) after the preparation of the MB and ML canals. However, in the MM canal, more pronounced transportation was detected in the PTG group at 2 mm below furcation, and in the TF group at 3 mm below furcation as compared with the other 2 systems (both p < 0.05). CONCLUSIONS: 3D printed tooth replicas have the advantages of consistency and can be an ideal model to evaluate the shaping ability of different instruments in the MM canal. OS and TF files performed similarly and both are appropriate for shaping the MM canal, while PTG may cause excessive and uneven resin removal, especially near the furcation, and may lead to root fragility and procedural errors.

Integrating X-ray phase-contrast imaging and histology for comparative evaluation of breast tissue malignancies in virtual histology analysis.

Detecting breast tissue alterations is essential for cancer diagnosis. However, inherent bidimensionality limits histological procedures' effectiveness in identifying these changes. Our study applies a 3D virtual histology method based on X-ray phase-contrast microtomography (PhC µ CT), performed at a synchrotron facility, to investigate breast tissue samples including different types of lesions, namely intraductal papilloma, micropapillary intracystic carcinoma, and invasive lobular carcinoma. One-to-one comparisons of X-ray and histological images explore the clinical potential of 3D X-ray virtual histology. Results show that PhC µ CT technique provides high spatial resolution and soft tissue sensitivity, while being non-destructive, not requiring a dedicated sample processing and being compatible with conventional histology. PhC µ CT can enhance the visualization of morphological characteristics such as stromal tissue, fibrovascular core, terminal duct lobular unit, stromal/epithelium interface, basement membrane, and adipocytes. Despite not reaching the (sub) cellular level, the three-dimensionality of PhC µ CT images allows to depict in-depth alterations of the breast tissues, potentially revealing pathologically relevant details missed by a single histological section. Compared to serial sectioning, PhC µ CT allows the virtual investigation of the sample volume along any orientation, possibly guiding the pathologist in the choice of the most suitable cutting plane. Overall, PhC µ CT virtual histology holds great promise as a tool adding to conventional histology for improving efficiency, accessibility, and diagnostic accuracy of pathological evaluation.

Postmortem imaging of fetuses at early gestations: A comparison of microfocus computed tomography with postmortem magnetic resonance at 9.4 T and postmortem ultrasound.

OBJECTIVE: To compare the diagnostic performance of postmortem ultrasound (PMUS), 9.4 T magnetic resonance imaging (MRI) and microfocus computed tomography (micro-CT) for the examination of early gestation fetuses. METHOD: Eight unselected fetuses (10-15 weeks gestational age) underwent at least 2 of the 3 listed imaging examinations. Six fetuses underwent 9.4 T MRI, four underwent micro-CT and six underwent PMUS. All operators were blinded to clinical history. All imaging was reported according to a prespecified template assessing 36 anatomical structures, later grouped into five regions: brain, thorax, heart, abdomen and genito-urinary. RESULTS: More anatomical structures were seen on 9.4 T MRI and micro-CT than with PMUS, with a combined frequency of identified structures of 91.9% and 69.7% versus 54.5% and 59.6 (p < 0.001; p < 0.05) respectively according to comparison groups. In comparison with 9.4 T MRI, more structures were seen on micro-CT (90.2% vs. 83.3%, p < 0.05). Anatomical structures were described as abnormal on PMUS in 2.7%, 9.4 T MRI in 6.1% and micro-CT 7.7% of all structures observed. However, the accuracy test could not be calculated because conventional autopsy was performed on 6 fetuses of that only one structure was abnormal. CONCLUSION: Micro-CT appears to offer the greatest potential as an imaging adjunct or non-invasive alternative for conventional autopsies in early gestation fetuses.

A novel micro-CT analysis for evaluating the regenerative potential of bone augmentation xenografts in rabbit calvarias.

Guided Bone Regeneration is a common procedure, yet, as new grafting materials are being introduced into the market, a reliable evaluation method is required. Critical size defect in animal models provides an accurate simulation, followed by histological sections to evaluate the new bone formation. However, histology is destructive, two-dimensional and technique-sensitive. In this study we developed a novel volumetric Micro-CT analysis to quantify new bone formation characteristics. Eight adult female New Zealand white rabbits were subjected to calvarial critical-size defects. Four 8 mm in diameter circular defects were preformed in each animal, to allow random allocation of four treatment modalities. All calvarias were scanned using Micro-CT. Each defect was segmented into four equal parts: pristine bone, outer, middle, and inner. Amira software (v. 6.3, www.fei.com ) was used to calculate the new bone volume in each region and compare it to that of the pristine bone. All grafting materials demonstrated that new bone formation decreased as it moved inward. Only the inner region differed across grafting materials (p = 0.001). The new Micro-CT analysis allowed us to divide each defect into 3D regions providing better understanding of the bone formation process. Amongst the various advantages of the Micro-CT, it enables us to quantify the graft materials and the newly formed bone independently, and to describe the defect morphology in 3D (bi- vs. uni-cortical defects). Providing an insight into the inner region of the defect can better predict the regenerative potential of the bone augmentation graft material. Therefore, the suggested Micro-CT analysis is beneficial for further developing of clinical approaches.

From breast cancer cell homing to the onset of early bone metastasis: The role of bone (re)modeling in early lesion formation.

Breast cancer often metastasizes to bone, causing osteolytic lesions. Structural and biophysical changes are rarely studied yet are hypothesized to influence metastasis. We developed a mouse model of early bone metastasis and multimodal imaging to quantify cancer cell homing, bone (re)modeling, and onset of metastasis. Using tissue clearing and three-dimensional (3D) light sheet fluorescence microscopy, we located enhanced green fluorescent protein-positive cancer cells and small clusters in intact bones and quantified their size and spatial distribution. We detected early bone lesions using in vivo microcomputed tomography (microCT)-based time-lapse morphometry and revealed altered bone (re)modeling in the absence of detectable lesions. With a new microCT image analysis tool, we tracked the growth of early lesions over time. We showed that cancer cells home in all bone compartments, while osteolytic lesions are only detected in the metaphysis, a region of high (re)modeling. Our study suggests that higher rates of (re)modeling act as a driver of lesion formation during early metastasis.

Accuracy of photon-counting computed tomography for the measurement of bone quality in the knee.

Visualization and quantification of bone microarchitecture in the human knee allows gaining insight into normal bone structure, and into the structural changes occurring in the onset and progression of bone diseases such as osteoporosis and osteoarthritis. However, current imaging modalities have limitations in capturing the intricacies of bone microarchitecture. Photon counting computed tomography (PCCT) is a promising imaging modality that presents high-resolution three-dimensional visualization of bone with a large field of view. However, the potential of PCCT in assessing trabecular microstructure has not been investigated yet. Therefore, this study aimed to evaluate the accuracy of PCCT in quantifying bone microstructure and bone mechanics in the knee. Five human cadaveric knees were scanned ex vivo using a PCCT scanner (Naetom alpha, Siemens, Germany) with an in-plane resolution of 146.5 µm and slice thickness of 100 µm. To assess accuracy, the specimens were also scanned with a high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT II, Scanco Medical, Switzerland) with a nominal isotropic voxel size of 60.7 µm as well as with micro-computed tomography (micro-CT; TESCAN UniTOM XL, Czech Republic) with a nominal isotropic voxel size of 25 µm which can be considered gold standards for in vivo and ex vivo scanning, respectively. The thickness and porosity of the subchondral bone and the microstructure of the underlying trabecular bone were assessed in the load bearing regions of the proximal tibia and distal femur. The apparent Young's modulus was determined by micro-finite element (µFE) analysis of subchondral trabecular bone (STB) in the load bearing regions of the proximal tibia using PCCT, HR-pQCT and micro-CT images. The correlation between PCCT measurements and micro-CT and HR-pQCT, respectively, was calculated. The coefficients of determination (R2) between PCCT and micro-CT based parameters, ranged from 0.69 to 0.87. The coefficients of determination between PCCT and HR-pQCT were slightly higher and ranged from 0.71 to 0.91. Apparent Young's modulus, assessed by µFE analysis of PCCT images, correlated well with that of micro-CT (R2 = 0.80, mean relative difference = 19 %). However, PCCT overestimated the apparent Young's modulus by 47 %, but the correlation (R2 = 0.84) remained strong when compared to HR-pQCT. The results of this study suggest that PCCT can be used to quantify bone microstructure in the knee.

The effect of root canal preparation tapers on planktonic bacteria and biofilm reduction in the apical third: A correlative microtomography and microbiological laboratory study.

AIM: To evaluate the influence of different preparation tapers on the reduction in planktonic bacteria and biofilms of Enterococcus faecalis and Candida albicans in the apical third (4 mm) of the mesial roots of mandibular molars, correlating decontamination with canal shape. METHODOLOGY: After microtomography analysis for morphological standardization of the canals, 48 mandibular molar roots, each containing two canals (96 canals), were contaminated with E. faecalis and C. albicans and divided into four groups (n = 11) for canal instrumentation using ProDesign Logic 2 files with different tapers G (.03): # 25.03; G (.04): # 25.04; G (.05): # 25.05; and G (.06): # 25.06 and irrigation with 2.5% sodium hypochlorite. Four roots were examined under a scanning electron microscope (SEM) to qualitatively assess biofilm formation. Eight roots were used as the negative control group (samples were not contaminated). Bacteriological samples were taken exclusively from the apical third of the roots before and after chemical-mechanical preparation and bacterial counts were determined (CFU/mL). The final micro-CT scan was used to quantify the volume variation and unprepared canal area in the apical third. Statistical analysis was performed using the Kruskal-Wallis, Student-Newman-Keuls and Wilcoxon tests for analysis of microbiological data. anova and the Tukey or Games-Howell test were used for analysis of micro-CT data and Spearman's test for correlations (α = 5%). RESULTS: All groups showed a significant reduction in bacteria (p < .05), with no statistically significant difference between groups. There was no significant difference in per cent volume increase between groups. The unprepared area (Δ%) was affected by the file used (p = .026) and was significantly lower for G (.06) compared to G (.03). There was no statistically significant correlation among bacterial reduction, volume and unprepared area (p > .05). CONCLUSION: The different preparation tapers influenced root canal shaping in the apical third but did not improve decontamination in this region.

Multiscale investigation of pore structure heterogeneity in carbonate rocks using digital imaging and SCAL measurements: A case study from Upper Jurassic limestones, Abu Dhabi, UAE.

This study presents a comprehensive analysis of rock properties for a selected group of six carbonate reservoir rock samples revealing complex structures at various length scales. Experimental laboratory methods as well as image analysis techniques were conducted in this study to characterize the macro- and micro-pores in mud- and grain-dominated limestones samples from the Upper Jurassic Arab Formation (Arab D member). Mercury Injection Capillary Pressure (MICP), porosimeter, and permeameter lab measurements were employed to assess the pore network heterogeneity and complexity. In addition, a multiscale rock imaging approach was implemented to detect grain and pore phases at several length scales using Thin Sections (TS), Scanning Electron Microscopy (SEM), Focused Ion Beam Scanning Electron Microscopy (FIB-SEM), as well as 3D X-ray Computed Tomography (CT), and micro-computed tomography images (MCT). Furthermore, the multifractal analysis method was applied on the MICP and FIB-SEM to characterize quantitatively the heterogeneity of the pores in the studied samples. Heterogeneous samples 3R, 4M, 5W, and 6M display the highest non-uniformity degree Δα values, falling within the range of [1.21, 1.39] based on FIB-SEM images. Samples 1G, 2R, 3R, and 5W exhibit more heterogeneous pore structure, with Δα values ranging from 0.73 to 1.49 based on the MICP experiments. The results and findings confirm the effectiveness of multifractal parameters Δα and the asymmetry degree in the vertical axis Δf(α) in quantifying and characterizing rock heterogeneity.

The Impact of Coronal Flaring Files on Pericervical Dentin Thickness in Mandibular Molars.

INTRODUCTION: This study aimed to assess the influence of different coronal flaring files on dentin removal in mandibular teeth using cone-beam computed tomographic (CBCT) images. METHODS: CBCT images of 48 mandibular molar teeth were acquired and randomly divided into 2 main groups, with each main group further divided into 3 subgroups. In the first main group, root canal preparation was performed using TruNatomy (Dentsply Sirona, Ballaigues, Switzerland), ProTaper Gold (Dentsply Sirona), and One Curve (Micro-Mega, Besancon, France) files without the use of coronal flaring files. In the second main group, root canal preparation was performed using the same files with the use of coronal flaring files. After the completion of root canal preparation, a second set of CBCT images was obtained. Subsequently, the dentin removal and remaining critical dentin were assessed by measuring at 4 distinct points below the furcation level. Data were compared between groups using the Mann-Whitney U and Kruskal-Wallis tests with alpha set at 5%. RESULTS: The ProTaper Gold files demonstrated higher dentin removal compared with the TruNatomy files. In the no-flaring groups, the One Curve files exhibited greater dentin removal than the TruNatomy files at specific levels. The use of coronal flaring files generally did not significantly impact dentin removal, except for certain cases in the TruNatomy and ProTaper Gold groups. CONCLUSIONS: The TruNatomy instrument group was more effective in preserving pericervical dentin compared with the other instrument groups. Coronal flaring files can be confidently used to preserve critical dentin during root canal treatment.

Micro-CT and high-field MRI for studying very early post-mortem human fetal anatomy at 8 weeks of gestation.

OBJECTIVE: This study involved very early post-mortem (PM) examination of human fetal anatomy at 8 weeks of gestation (WG) using whole-body multimodal micro-imaging: micro-CT and high-field MRI (HF-MRI). We discuss the potential place of this imaging in early first-trimester virtual autopsy. METHODS: We performed micro-CT after different contrast-bath protocols including diffusible iodine-based contrast-enhanced (dice) and HF-MRI with a 9.4 T machine with qualitative and quantitative evaluation and obtained histological sections. RESULTS: Nine fetuses were included: the crown-rump length was 10-24 mm and corresponded to 7 and 9 WG according to the Robinson formula. The Carnegie stages were 17-21. Dice micro-CT and HF-MRI presented high signal to noise ratio, >5, according to the Rose criterion, and for allowed anatomical phenotyping in these specimens. Imaging did not alter the histology, allowing immunostaining and pathological examination. CONCLUSION: PM non-destructive whole-body multimodal micro-imaging: dice micro-CT and HF-MRI allows for PM human fetal anatomy study as early as 8 WG. It paves the way to virtual autopsy in the very early first trimester. Obtaining a precision phenotype, even regarding miscarriage products, allows a reverse phenotyping to select variants of interest in genome-wide analysis, offering potential genetic counseling for bereaved parents.

Surgical Considerations in Inner Ear Gene Therapy from Human Temporal Bone Anatomy.

OBJECTIVE(S): Recently directed methods of inner ear drug delivery underscore the necessity for understanding critical anatomical dimensions. This study examines anatomical measurements of the human middle and inner ear relevant for inner ear drug delivery studied with three different imaging modalities. METHODS: Post-mortem human temporal bones were analyzed using human temporal bone histopathology (N = 24), micro computerized tomography (µCT; N = 4), and synchrotron radiation phase-contrast imaging (SR-PCI; N = 7). Nine measurements involving the oval and round windows were performed when relevant anatomical structures were visualized for subsequent age-controlled analysis, and comparisons were made between imaging methods. RESULTS: Combined human temporal bone histopathology showed the mean distance to the saccule from the center of the stapes footplate (FP) was 2.07 ± 0.357 mm and the minimum distance was 1.23 mm. The mean distance from the round window membrane (RWM) to the osseous spiral lamina (OSL) was 1.75 ± 0.199 mm and the minimum distance was 1.43 mm. Instruments inserted up to 1 mm past the center of the FP are unlikely to cause saccular damage, provided there are no endolymphatic hydrops. Similarly, instruments inserted up to 1 mm through the RWM in the trajectory toward the OSL are unlikely to cause OSL damage. CONCLUSION: The combined analyses of inner-ear dimensions of age-controlled groups and imaging modalities demonstrate critical dimensions of importance to consider when inserting delivery vehicles into the human cochlea. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:2879-2888, 2024.

Flatsonic Ultrasonic Tip Optimizes the Removal of Remaining Filling Material in Flattened Root Canals: A Micro-computed Tomographic Analysis.

INTRODUCTION: The aim of this study was to evaluate the effectiveness of the XP-endo Finisher R (XPFR; FKG Dentaire, La Chaux-de-Fonds, Switzerland) or the Flatsonic ultrasonic tip (Helse Ultrasonic, Santa Rosa de Viterbo, SP, Brazil) in removing remaining filling material after the retreatment of flattened root canals using micro-computed tomographic imaging. METHODS: Twenty-four flattened distal root canals of mandibular molars with a buccolingual diameter 4 or more times larger than the mesiodistal diameter were prepared with Reciproc Blue (RB) R40 (VDW GmbH, Munich, Germany) and filled using the Tagger hybrid technique. All canals were retreated with RB R40, and apical enlargement was performed with RB R50 (VDW GmbH). The specimens were randomly distributed into 2 groups: XPFR or Flatsonic (n = 12). The percentage of remaining filling material after retreatment and centralization ability was evaluated. Data were submitted to Mann-Whitney, Wilcoxon, and unpaired t tests (α = 5%). RESULTS: Greater capacity to remove remaining filling material in the entire canal and the cervical and middle thirds was observed for the Flatsonic compared with the XPFR (P < .05). However, both supplementary cleaning techniques showed a similar percentage of residual filling material in the apical third (P > .05). No difference was observed in the centralization ability between the techniques (P > .05). CONCLUSIONS: The Flatsonic promotes greater removal of remaining filling material than the XPFR in the retreatment of flattened root canals. However, both supplementary cleaning approaches were similar in the apical third. The XPFR and Flatsonic were able to maintain root canal centralization.

Use of micro-computed tomography and scanning electron microscopy with energy-dispersive spectroscopy to distinguish natural white spot enamel lesions from sound enamel in human premolars.

PURPOSE: The aim of the present study was to develop a novel method for distinguishing white spot lesions (WSLs) from sound enamel in human premolars using micro-computed tomography (micro-CT) and scanning electron microscopy (SEM) with energy-dispersive spectroscopy (EDS), and to examine differences in surface morphology, chemical composition, and mineral density (MD) between these two areas. METHODS: Fourteen premolars with natural WSLs on the enamel surface of the crowns were examined. After sectioning the teeth, each specimen containing WSLs adjacent to intact enamel was examined for MD, surface morphology, and atomic percentages (At%) of chemical components using micro-CT and SEM/EDS, respectively. Differences between these areas of the same specimen were analyzed statistically using paired t-test. RESULTS: SEM images highlighted increased roughness and irregularity in the lesion area. EDS analysis revealed significant reductions in calcium (Ca), phosphorus (P), fluorine (F), chlorine (Cl), and sodium (Na) levels at the lesion surface in comparison to intact enamel (P < 0.05). The decreases in the MD of the lesions were statistically significant in comparison to sound enamel (P < 0.05). CONCLUSION: These findings provide standard measurements for evaluating the essential characteristics of WSLs and intact enamel, being vital for assessment of treatment outcomes and development of innovative biomaterials for management of hypo-mineralized enamel lesions.