Deep Convolutional Neural Networks Provide Motion Grading for High-Resolution Peripheral Quantitative Computed Tomography of the Scaphoid.

In vivo high-resolution peripheral quantitative computed tomography (HR-pQCT) studies on bone characteristics are limited, partly due to the lack of standardized and objective techniques to describe motion artifacts responsible for lower-quality images. This study investigates the ability of such deep-learning techniques to assess image quality in HR-pQCT datasets of human scaphoids. In total, 1451 stacks of 482 scaphoid images from 53 patients, each with up to six follow-ups within one year, and each with one non-displaced fractured and one contralateral intact scaphoid, were independently graded by three observers using a visual grading scale for motion artifacts. A 3D-CNN was used to assess image quality. The accuracy of the 3D-CNN to assess the image quality compared to the mean results of three skilled operators was between 92% and 96%. The 3D-CNN classifier reached an ROC-AUC score of 0.94. The average assessment time for one scaphoid was 2.5 s. This study demonstrates that a deep-learning approach for rating radiological image quality provides objective assessments of motion grading for the scaphoid with a high accuracy and a short assessment time. In the future, such a 3D-CNN approach can be used as a resource-saving and cost-effective tool to classify the image quality of HR-pQCT datasets in a reliable, reproducible and objective way.

Influence of demographic factors on the occurrence of motion artefacts in HR-pQCT.

The study shows a high incidence of motion artefacts in a central European population and a significant increase of those artefacts with higher age. These findings may impact on the design and conduct of future in vivo HR-pQCT studies or at least help to estimate the potential number of drop outs due to unusable image quality. PURPOSE: Motion artefacts in high-resolution peripheral quantitative computed tomography (HR-pQCT) are challenging, as they introduce error into the resulting measurement data. The aim of this study was to assess the general occurrence of motion artefacts in healthy distal radius and to evaluate the influence of demographic factors. METHODS: The retrospective study is based on 525 distal radius second-generation HR-pQCT scans of 95 patients. All stacks were evaluated by two experienced observers and graded according to the visual grading scale recommended by the manufacturer, ranging from grade 1 (no visible motion artefacts) to grade 5 (severe motion artefacts). Correlations between demographic factors and image quality were evaluated using a linear mixed effects model analysis. RESULTS: The average visual grading was 2.7 (SD ± 0.7). Age and severity of motion artefacts significantly correlated (p = 0.026). Patients aged 65 years or above had an average image quality between grades 1 and 3 in 72.7% of cases, while patients younger than 65 had an average image quality between grades 1 and 3 in 91.9% of cases. Gender, smoking behaviour, and handedness had no significant influence on motion artefacts. CONCLUSION: This study showed a high incidence of motion artefacts in a representative central European population, but also a significant increase of motion artefacts with higher age. This could impact further study designs by planning for a sufficiently large and if possible a more selective study population to gain a representative amount of high-quality image data.

Tunnel widening after ACL reconstruction with different fixation techniques: aperture fixation with biodegradable interference screws versus all-inside technique with suspensory cortical buttons. 5-year data from a prospective randomized trial.

BACKGROUND: The aim of the present study was to examine tunnel widening and clinical outcomes after anterior cruciate ligament reconstruction (ACLR) using two different fixation methods: aperture fixation with biodegradable interference screws versus all-inside ACLR with suspensory cortical buttons. METHODS: Tunnel widening was assessed using volumetric and diameter measurements on magnetic resonance imaging (MRI) scans directly after surgery, as well as 6 months and 2 and 5 years postoperatively. Clinical outcomes were assessed after 5 years with instrumented tibial anteroposterior translation measurement (KT-1000), single-leg hop testing, and the IKDC, Lysholm, and Tegner activity scores. RESULTS: At the final follow-up, the study population consisted of 21 patients, 12 of whom underwent screw fixation and 9 of whom had button fixation. 3 patients with all-inside ACLR had sustained early repeat ruptures within 6 months after surgery and had to be excluded from the further analysis. With screw fixation, the tibial tunnel volume changed significantly more over time compared to all-inside button fixation, with a larger initial increase at 6 months (from postoperative 2.9 ± 0.2 to 3.3 ± 0.2 cm3 at 6 months versus 1.7 ± 0.1 to 1.9 ± 0.2 cm3) and a greater final decrease over 2-5 years postoperatively (from 3.1 ± 0.2 to 1.9 ± 0.2 cm3 versus 1.8 ± 0.2 ± 0.1 to 1.3 ± 0.1 cm3) (P < 0.001). The femoral tunnel volume remained comparable between the two groups throughout the follow-up period, with an initial 1.6 ± 0.1 cm3 in both groups and 1.2 ± 0.1 vs. 1.3 ± 0.1 after 5 years in the screw and button groups, respectively (P ≥ 0.314). The maximum tibial and femoral tunnel diameters were significantly larger with screw fixation at all four time points. Tibial diameters measured 11.1 ± 0.2, 12.3 ± 0.3, 12.3 ± 0.4, and 11.2 ± 0.4 mm in the screw group versus 8.1 ± 0.3, 8.9 ± 0.3, 9.1 ± 0.4 and 8.2 ± 0.5 mm in the button group (P < 0.001). Femoral diameters measured 8.6 ± 0.2, 10.5 ± 0.4, 10.2 ± 0.3, and 8.9 ± 0.3 versus 7.3 ± 0.3, 8.4 ± 0.4, 8.4 ± 0.3, 7.5 ± 0.3, respectively (P ≤ 0.007). Four patients (33%) in the screw group exceeded a diameter of 12 mm on the tibial side after 5 years versus none in the button group (not significant, P = 0.104). Tibial anteroposterior translation measurement with KT-1000 after 5 years was 2.3 ± 2.4 mm in the screw group versus 3.2 ± 3.5 mm in the button group (not significant, P = 0.602). There were no significant differences between the groups in any of the other clinical outcomes. CONCLUSION: Tibial tunnels in ACLR with screw fixation were associated with a larger increase in tunnel volume within the first 2 years and a greater decrease up to 5 years after surgery, while femoral tunnel volumes did not differ significantly. On the tibial side, the need for staged revision ACLR may be greater after biodegradable interference screw fixation if repeat ruptures occur, especially within the first 2 years after primary ACLR. Concerns may remain regarding a higher graft failure rate with all-inside ACLR. LEVEL OF EVIDENCE: II. RCT CONSORT: NCT01755819.

The negative adipogenesis regulator Dlk1 is transcriptionally regulated by Ifrd1 (TIS7) and translationally by its orthologue Ifrd2 (SKMc15).

Delta-like homolog 1 (Dlk1), an inhibitor of adipogenesis, controls the cell fate of adipocyte progenitors. Experimental data presented here identify two independent regulatory mechanisms, transcriptional and translational, by which Ifrd1 (TIS7) and its orthologue Ifrd2 (SKMc15) regulate Dlk1 levels. Mice deficient in both Ifrd1 and Ifrd2 (dKO) had severely reduced adipose tissue and were resistant to high-fat diet-induced obesity. Wnt signaling, a negative regulator of adipocyte differentiation, was significantly upregulated in dKO mice. Elevated levels of the Wnt/ß-catenin target protein Dlk1 inhibited the expression of adipogenesis regulators Pparg and Cebpa, and fatty acid transporter Cd36. Although both Ifrd1 and Ifrd2 contributed to this phenotype, they utilized two different mechanisms. Ifrd1 acted by controlling Wnt signaling and thereby transcriptional regulation of Dlk1. On the other hand, distinctive experimental evidence showed that Ifrd2 acts as a general translational inhibitor significantly affecting Dlk1 protein levels. Novel mechanisms of Dlk1 regulation in adipocyte differentiation involving Ifrd1 and Ifrd2 are based on experimental data presented here.

Toll-Like Receptor 3 Mediates Aortic Stenosis Through a Conserved Mechanism of Calcification.

BACKGROUND: Calcific aortic valve disease (CAVD) is characterized by a phenotypic switch of valvular interstitial cells to bone-forming cells. Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors at the interface between innate immunity and tissue repair. Type I interferons (IFNs) are not only crucial for an adequate antiviral response but also implicated in bone formation. We hypothesized that the accumulation of endogenous TLR3 ligands in the valvular leaflets may promote the generation of osteoblast-like cells through enhanced type I IFN signaling. METHODS: Human valvular interstitial cells isolated from aortic valves were challenged with mechanical strain or synthetic TLR3 agonists and analyzed for bone formation, gene expression profiles, and IFN signaling pathways. Different inhibitors were used to delineate the engaged signaling pathways. Moreover, we screened a variety of potential lipids and proteoglycans known to accumulate in CAVD lesions as potential TLR3 ligands. Ligand-receptor interactions were characterized by in silico modeling and verified through immunoprecipitation experiments. Biglycan (Bgn), Tlr3, and IFN-α/ß receptor alpha chain (Ifnar1)-deficient mice and a specific zebrafish model were used to study the implication of the biglycan (BGN)-TLR3-IFN axis in both CAVD and bone formation in vivo. Two large-scale cohorts (GERA [Genetic Epidemiology Research on Adult Health and Aging], n=55 192 with 3469 aortic stenosis cases; UK Biobank, n=257 231 with 2213 aortic stenosis cases) were examined for genetic variation at genes implicated in BGN-TLR3-IFN signaling associating with CAVD in humans. RESULTS: Here, we identify TLR3 as a central molecular regulator of calcification in valvular interstitial cells and unravel BGN as a new endogenous agonist of TLR3. Posttranslational BGN maturation by xylosyltransferase 1 (XYLT1) is required for TLR3 activation. Moreover, BGN induces the transdifferentiation of valvular interstitial cells into bone-forming osteoblasts through the TLR3-dependent induction of type I IFNs. It is intriguing that Bgn-/-, Tlr3-/-, and Ifnar1-/- mice are protected against CAVD and display impaired bone formation. Meta-analysis of 2 large-scale cohorts with >300 000 individuals reveals that genetic variation at loci relevant to the XYLT1-BGN-TLR3-interferon-α/ß receptor alpha chain (IFNAR) 1 pathway is associated with CAVD in humans. CONCLUSIONS: This study identifies the BGN-TLR3-IFNAR1 axis as an evolutionarily conserved pathway governing calcification of the aortic valve and reveals a potential therapeutic target to prevent CAVD.

The impact of motion induced artifacts in the evaluation of HR-pQCT scans of the scaphoid bone: an assessment of inter- and intraobserver variability and quantitative parameters.

Background: In-vivo high-resolution peripheral quantitative computed tomography (HR-pQCT) has high potential in scaphoid bone pathologies' scientific and clinical fields. The manufacturer's visual grading scale (VGS) classifies motion artifacts and divides scans into five quality grades ranging from grade 1 (good quality) to grade 5 (poor quality). This prospective study aimed to investigate the feasibility of the VGS and the influence of image quality on bone density and microarchitecture parameters for the scaphoid bone. Methods: Within one year, twenty-two patients with scaphoid fractures received up to six scans of their fractured and contralateral wrist (each consisting of three stacks) using second-generation HR-pQCT (total 256 scans). Three experienced observers graded each stack following the visual grading system, and inter- and intraobserver variability were assessed. The contralateral uninjured scaphoids were then compared pairwise within each patient to high-quality grade 1 scans to determine the influence of image quality on density and microarchitecture parameters. Results: Inter- and intraobserver variability among the three observers significantly revealed fair to moderate agreement, P<0.001 and P<0.05, respectively. Bone volume (BV) fraction tended to increase with poorer image quality but did not exceed four percent. Trabecular bone mineral density (Tb.BMD) decreased with poorer image quality but did not exceed five percent. Trabecular number and trabecular thickness significantly increased by 15.5% and 6.8% at grade five (P<0.001), respectively, and trabecular separation significantly decreased by 13.7% at grade five (P<0.001). Conclusions: This study revealed a considerable influence of motion on bone morphometry parameters of the scaphoid. Therefore, high image quality must be a central point in studies focusing on the histomorphometry of small objects. The high inter- and intraobserver variability limit the VGS. Future research may focus on other grading systems or automated techniques leading to more consistent and reproducible results. Currently, the use of microarchitectural analysis should be limited to cases without motion artefacts or, at most low graded motion artefacts.

Morphological and Tissue Characterization with 3D Reconstruction of a 350-Year-Old Austrian Ardea purpurea Glacier Mummy.

Glaciers are dwindling archives, releasing animal mummies preserved in the ice for centuries due to climate changes. As preservation varies, residual soft tissues may differently expand the biological information content of such mummies. DNA studies have proven the possibility of extracting and analyzing DNA preserved in skeletal residuals and sediments for hundreds or thousands of years. Paleoradiology is the method of choice as a non-destructive tool for analyzing mummies, including micro-computed tomography (micro-CT) and magnetic resonance imaging (MRI). Together with radiocarbon dating, histo-anatomical analyses, and DNA sequencing, these techniques were employed to identify a 350-year-old Austrian Ardea purpurea glacier mummy from the Ötztal Alps. Combining these techniques proved to be a robust methodological concept for collecting inaccessible information regarding the structural organization of the mummy. The variety of methodological approaches resulted in a distinct picture of the morphological patterns of the glacier animal mummy. The BLAST search in GenBank resulted in a 100% and 98.7% match in the cytb gene sequence with two entries of the species Purple heron (Ardea purpurea; Accession number KJ941160.1 and KJ190948.1) and a 98% match with the same species for the 16 s sequence (KJ190948.1), which was confirmed by the anatomic characteristics deduced from micro-CT and MRI.

As low as diagnostically acceptable dose imaging in maxillofacial trauma: a reference quality approach.

OBJECTIVES: As-low-as-diagnostically-acceptable (ALADA) doses are substantially lower than current diagnostic reference levels. To improve dose management, a reference quality approach was tested in which phantom quality metrics of a clinical ALADA dose reference protocol were used to benchmark potential ALADA dose protocols for various scanner models. METHODS: Spatial resolution, contrast resolution, contrast-to-noise ratio (CNR) and subjective noise and sharpness were evaluated for a clinical ALADA dose reference protocol at 80 kV and 40 mA (CTDIvol 2.66 mGy) and compared with test protocols of two CT scanners at 100 kV and 35 mA (3.08-3.44 mGy), 80 kV and 54-61 mA (2.65 mGy), 80 kV and 40 mA (1.73-1.92 mGy), and 80 kV and 21-23 mA (1.00-1.03 mGy) using different kernels, filtered backprojection and iterative reconstructions. The test protocols with the lowest dose showing quality metrics non-inferior to the reference protocol were verified in a cadaver study by determining the diagnostic accuracy of detection of maxillofacial fractures and CNR of the optical nerve and rectus inferior muscle. RESULTS: 36 different image series were analysed in the phantom study. Based on the phantom quality metrics, potential ALADA dose protocols at 1.73-1.92 mGy were selected. Compared with the reference images, the selected protocols showed non-inferiority in the detection and classification of maxillofacial fractures and non-inferior CNR of orbital soft tissues in the cadaver study. CONCLUSIONS: Reference quality metrics from clinical ALADA dose protocols may be used to guide selection of potential ALADA dose protocols of different CT scanners.

Characterizing the Mechanical Behavior of Bone and Bone Surrogates in Compression Using pQCT.

Many axial and appendicular skeleton bones are subjected to repetitive loading during daily activities. Until recently, the structural analysis of fractures has been limited to 2D sections, and the dynamic assessment of fracture progression has not been possible. The structural failure was analyzed using step-wise micro-compression combined with time-lapsed micro-computed tomographic imaging. The structural failure was investigated in four different sample materials (two different bone surrogates, lumbar vertebral bodies from bovine and red deer). The samples were loaded in different force steps based on uniaxial compression tests. The micro-tomography images were used to create three-dimensional models from which various parameters were calculated that provide information about the structure and density of the samples. By superimposing two 3D images and calculating the different surfaces, it was possible to precisely analyze which trabeculae failed in which area and under which load. According to the current state of the art, bone mineral density is usually used as a value for bone quality, but the question can be raised as to whether other values such as trabecular structure, damage accumulation, and bone mineralization can predict structural competence better than bone mineral density alone.

Application of Micro-Computed Tomography for the Estimation of the Post-Mortem Interval of Human Skeletal Remains.

It is challenging to estimate the post-mortem interval (PMI) of skeletal remains within a forensic context. As a result of their interactions with the environment, bones undergo several chemical and physical changes after death. So far, multiple methods have been used to follow up on post-mortem changes. There is, however, no definitive way to estimate the PMI of skeletal remains. This research aimed to propose a methodology capable of estimating the PMI using micro-computed tomography measurements of 104 human skeletal remains with PMIs between one day and 2000 years. The present study indicates that micro-computed tomography could be considered an objective and precise method of PMI evaluation in forensic medicine. The measured parameters show a significant difference regarding the PMI for Cort Porosity p < 0.001, BV/TV p > 0.001, Mean1 p > 0.001 and Mean2 p > 0.005. Using a machine learning approach, the neural network showed an accuracy of 99% for distinguishing between samples with a PMI of less than 100 years and archaeological samples.

What controls the remobilization and deformation of surficial sediment by seismic shaking? Linking lacustrine slope stratigraphy to great earthquakes in South-Central Chile.

Remobilization and deformation of surficial subaqueous slope sediments create turbidites and soft sediment deformation structures, which are common features in many depositional records. Palaeoseismic studies have used seismically-induced turbidites and soft sediment deformation structures preserved in sedimentary sequences to reconstruct recurrence patterns and - in some cases - allow quantifying rupture location and magnitude of past earthquakes. However, current understanding of earthquake-triggered remobilization and deformation lacks studies targeting where these processes take place, the subaqueous slope and involving direct comparison of sedimentary fingerprint with well-documented historical earthquakes. This study investigates the sedimentary imprint of six megathrust earthquakes with varying rupture characteristics in 17 slope sediment cores from two Chilean lakes, Riñihue and Calafquén, and evaluates how it links to seismic intensity, peak ground acceleration, bracketed duration and slope angle. Centimetre-scale stratigraphic gaps ranging from ca 1 to 20 cm - caused by remobilization of surficial slope sediment - were identified using high-resolution multi-proxy core correlation of slope to basin cores, and six types of soft sediment deformation structures ranging from ca 1 to 25 cm thickness using high-resolution three-dimensional X-ray computed tomography data. Stratigraphic gaps occur on slope angles of ≥2.3°, whereas deformation already occurs from slope angle 0.2°. The thickness of both stratigraphic gaps and soft sediment deformation structures increases with slope angle, suggesting that increased gravitational shear stress promotes both surficial remobilization and deformation. Seismic shaking is the dominant trigger for surficial remobilization and deformation at the studied lakes. Total remobilization depth correlates best with bracketed duration and is highest in both lakes for the strongest earthquakes (M w ca 9.5). In lake Riñihue, soft sediment deformation structure thickness and type correlate best with peak ground acceleration providing the first field-based evidence of progressive soft sediment deformation structure development with increasing peak ground acceleration for soft sediment deformation structures caused by Kelvin-Helmholtz instability. The authors propose that long duration and low frequency content of seismic shaking favours surficial remobilization, whereas ground motion amplitude controls Kelvin-Helmholtz instability-related soft sediment deformation structure development.

ALADA Dose Optimization in the Computed Tomography of the Temporal Bone: The Diagnostic Potential of Different Low-Dose CT Protocols.

OBJECTIVE: Repeated computed tomography (CT) is essential for diagnosis, surgical planning and follow-up in patients with middle and inner ear pathology. Dose reduction to "as low as diagnostically acceptable" (ALADA) is preferable but challenging. We aimed to compare the diagnostic quality of images of subtle temporal bone structures produced with low doses (LD) and reference protocols (RP). METHODS: Two formalin-fixed human cadaver heads were scanned using a 64-slice CT scanner and cone-beam CT (CBCT). The protocols were: RP (120 kV, 250 mA, CTDIvol 83.72 mGy), LD1 (100 kV, 80 mA, CTDIvol 26.79 mGy), LD2 (100 kV, 35 mA, CTDIvol 7.66 mGy), LD3 (80 kV, 40 mA, CTDIvol 4.82 mGy), and CBCT standard protocol. Temporal bone structures were assessed using a 5-point scale. RESULTS: A median score of ≥2 was achieved with protocols such as the tendons of m. tensor tympani (RP/LD1/LD2/CBCT) and m. stapedius (CBCT), the incudostapedial joint (RP/LD1/CBCT), the incudomalleolar joint (RP/LD1/LD2/CBCT), the stapes feet (RP/LD1/CBCT), the stapes head (RP/LD1/LD2/CBCT), the tympanic membrane (RP/LD1/LD2/CBCT), the lamina spiralis ossea (none), the chorda tympani (RP/LD1/CBCT), and the modiolus (RP/LD1/LD2/CBCT). Adaptive statistical iterative reconstructions did not show advantages over the filtered back projection. CONCLUSIONS: LD protocols using a CTDIvol of 7.66 mGy may be sufficient for the identification of temporal bone structures.

Protective effects of spironolactone on vascular calcification in chronic kidney disease.

BACKGROUND: Vascular calcification is common in chronic kidney disease (CKD) and associated with increased cardiovascular mortality. Aldosterone has been implicated as an augmenting factor in the progression of vascular calcification. The present study further explored putative beneficial effects of aldosterone inhibition by the mineralocorticoid receptor antagonist spironolactone on vascular calcification in CKD. METHODS: Serum calcification propensity was determined in serum samples from the MiREnDa trial, a prospective, randomized controlled clinical trial to investigate efficacy and safety of spironolactone in maintenance hemodialysis patients. Experiments were conducted in mice with subtotal nephrectomy and cholecalciferol treatment, and in calcifying primary human aortic smooth muscle cells (HAoSMCs). RESULTS: Serum calcification propensity was improved by spironolactone treatment in patients on hemodialysis from the MiREnDa trial. In mouse models and HAoSMCs, spironolactone treatment ameliorated vascular calcification and expression of osteogenic markers. CONCLUSIONS: These observations support a putative benefit of spironolactone treatment in CKD-associated vascular calcification. Further research is required to investigate possible improvements in cardiovascular outcomes by spironolactone and whether the benefits outweigh the risks in patients with CKD.

Formation Dominates Resorption With Increasing Mineralized Density and Time Postfracture in Cortical but Not Trabecular Bone: A Longitudinal HRpQCT Imaging Study in the Distal Radius.

Clinical evaluation of fracture healing is often limited to an assessment of fracture bridging from radiographic images, without consideration for other aspects of bone quality. However, recent advances in HRpQCT offer methods to accurately monitor microstructural bone remodeling throughout the healing process. In this study, local bone formation and resorption were investigated during the first year post fracture in both the fractured (n = 22) and contralateral (n = 19) radii of 34 conservatively treated patients (24 female, 10 male) who presented with a unilateral radius fracture at the Innsbruck University Hospital, Austria. HRpQCT images and clinical metrics were acquired at six time points for each patient. The standard HRpQCT image acquisition was captured for all radii, with additional distal and proximal image acquisitions for the fractured radii. Measured radial bone densities were isolated with a voxel-based mask and images were rigidly registered to images from the previous imaging session using a pyramid-based approach. From the registered images, bone formation and resorption volume fractions were quantified for multiple density-based thresholds and compared between the fractured and contralateral radius and relative to demographics, bone morphometrics, and fracture metrics using regression. Compared with the contralateral radius, both bone formation and resorption were significantly increased in the fractured radius throughout the study for nearly all evaluated thresholds. Higher density cortical bone formation continually increased throughout the duration of the study and was significantly greater than resorption during late-stage healing in both the fractured and intact regions of the radius. With the small and diverse study population, only weak relationships between fracture remodeling and patient-specific parameters were unveiled. However this study provides methods for the analysis of local bone remodeling during fracture healing and highlights relevant considerations for future studies, specifically that remodeling postfracture is likely to continue beyond 12-months postfracture. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Measurement of the Intracochlear Hypothermia Distribution Utilizing Tympanic Cavity Hypothermic Rinsing Technique in a Cochlea Hypothermia Model.

Introduction: Cochlea implants can cause severe trauma leading to intracochlear apoptosis, fibrosis, and eventually to loss of residual hearing. Mild hypothermia has been shown to reduce toxic or mechanical noxious effects, which can result in inflammation and subsequent hearing loss. This paper evaluates the usability of standard surgical otologic rinsing as cooling medium during cochlea implantation as a potential hearing preservation technique. Material and Methods: Three human temporal bones were prepared following standard mastoidectomy and posterior tympanotomy. Applying a retrocochlear approach leaving the mastoidectomy side intact, temperature probes were placed into the basal turn (n = 4), the middle turn (n = 2), the helicotrema, and the modiolus. Temperature probe positions were visualized by microcomputed tomography (µCT) imaging and manually segmented using Amira® 7.6. Through the posterior tympanotomy, the tympanic cavity was rinsed at 37°C in the control group, at room temperature (in the range between 22 and 24°C), and at iced water conditions. Temperature changes were measured in the preheated temporal bone. In each temperature model, rinsing was done for 20 min at the pre-specified temperatures measured in 0.5-s intervals. At least five repetitions were performed. Data were statistically analyzed using pairwise t-tests with Bonferroni correction. Results: Steady-state conditions achieved in all three different temperature ranges were compared in periods between 150 and 300 s. Temperature in the inner ear started dropping within the initial 150 s. Temperature probes placed at basal turn, the helicotrema, and middle turn detected statistically significant fall in temperature levels following body temperature rinses. Irrigation at iced conditions lead to the most significant temperature drops. The curves during all measurements remained stable with 37°C rinses. Conclusion: Therapeutic hypothermia is achieved with standard surgical irrigation fluid, and temperature gradients are seen along the cochlea. Rinsing of 120 s duration results in a therapeutic local hypothermia throughout the cochlea. This otoprotective procedure can be easily realized in clinical practice.

Photoacoustic tomography of ex vivo mouse hearts with myocardial infarction.

In the present study, we evaluated the applicability of ex vivo photoacoustic imaging (PAI) on small animal organs. We used photoacoustic tomography (PAT) to visualize infarcted areas within murine hearts and compared these data to other imaging techniques [magnetic resonance imaging (MRI), micro-computed tomography] and histological slices. In order to induce ischemia, an in vivo ligation of the left anterior descending artery was performed on nine wild-type mice. After varying survival periods, the hearts were excised and fixed in formaldehyde. Samples were illuminated with nanosecond laser pulses delivered by a Nd:YAG pumped optical parametric oscillator. Ultrasound detection was achieved using a Mach-Zehnder interferometer (MZI) working as an integrating line detector. The voxel data were computed using a Fourier-domain based reconstruction algorithm, followed by inverse Radon transforms. The results clearly showed the capability of PAI to visualize myocardial infarction and to produce three-dimensional images with a spatial resolution of approximately 120 µm. Regions of affected muscle tissue in PAI corresponded well with the results of MRI and histology. Photoacoustic tomography utilizing a MZI for ultrasound detection allows for imaging of small tissue samples. Due to its high spatial resolution, good soft tissue contrast and comparatively low cost, PAT offers great potentials for imaging.