Automating three-dimensional osteoarthritis histopathological grading of human osteochondral tissue using machine learning on contrast-enhanced micro-computed tomography.

OBJECTIVE: To develop and validate a machine learning (ML) approach for automatic three-dimensional (3D) histopathological grading of osteochondral samples imaged with contrast-enhanced micro-computed tomography (CEµCT). DESIGN: A total of 79 osteochondral cores from 24 total knee arthroplasty patients and two asymptomatic donors were imaged using CEµCT with phosphotungstic acid -staining. Volumes-of-interest (VOI) in surface (SZ), deep (DZ) and calcified (CZ) zones were extracted depth-wise and subjected to dimensionally reduced Local Binary Pattern -textural feature analysis. Regularized linear and logistic regression (LR) models were trained zone-wise against the manually assessed semi-quantitative histopathological CEµCT grades (diameter = 2 mm samples). Models were validated using nested leave-one-out cross-validation and an independent test set (4 mm samples). The performance was primarily assessed using Mean Squared Error (MSE) and Average Precision (AP, confidence intervals are given in square brackets). RESULTS: Highest performance on cross-validation was observed for SZ, both on linear regression (MSE = 0.49, 0.69 and 0.71 for SZ, DZ and CZ, respectively) and LR (AP = 0.9 [0.77-0.99], 0.46 [0.28-0.67] and 0.65 [0.41-0.85] for SZ, DZ and CZ, respectively). The test set evaluations yielded increased MSE on all zones. For LR, the performance was also best for the SZ (AP = 0.85 [0.73-0.93], 0.82 [0.70-0.92] and 0.8 [0.67-0.9], for SZ, DZ and CZ, respectively). CONCLUSION: We present the first ML-based automatic 3D histopathological osteoarthritis (OA) grading method which also adequately perform on grading unseen data, especially in SZ. After further development, the method could potentially be applied by OA researchers since the grading software and all source codes are publicly available.

Quantifying Subresolution 3D Morphology of Bone with Clinical Computed Tomography.

The aim of this study was to quantify sub-resolution trabecular bone morphometrics, which are also related to osteoarthritis (OA), from clinical resolution cone beam computed tomography (CBCT). Samples (n = 53) were harvested from human tibiae (N = 4) and femora (N = 7). Grey-level co-occurrence matrix (GLCM) texture and histogram-based parameters were calculated from CBCT imaged trabecular bone data, and compared with the morphometric parameters quantified from micro-computed tomography. As a reference for OA severity, histological sections were subjected to OARSI histopathological grading. GLCM and histogram parameters were correlated to bone morphometrics and OARSI individually. Furthermore, a statistical model of combined GLCM/histogram parameters was generated to estimate the bone morphometrics. Several individual histogram and GLCM parameters had strong associations with various bone morphometrics (|r| > 0.7). The most prominent correlation was observed between the histogram mean and bone volume fraction (r = 0.907). The statistical model combining GLCM and histogram-parameters resulted in even better association with bone volume fraction determined from CBCT data (adjusted R2 change = 0.047). Histopathology showed mainly moderate associations with bone morphometrics (|r| > 0.4). In conclusion, we demonstrated that GLCM- and histogram-based parameters from CBCT imaged trabecular bone (ex vivo) are associated with sub-resolution morphometrics. Our results suggest that sub-resolution morphometrics can be estimated from clinical CBCT images, associations becoming even stronger when combining histogram and GLCM-based parameters.

Spectral entropy indicates electrophysiological and hemodynamic changes in drug-resistant epilepsy - A multimodal MREG study.

OBJECTIVE: Epilepsy causes measurable irregularity over a range of brain signal frequencies, as well as autonomic nervous system functions that modulate heart and respiratory rate variability. Imaging dynamic neuronal signals utilizing simultaneously acquired ultra-fast 10 Hz magnetic resonance encephalography (MREG), direct current electroencephalography (DC-EEG), and near-infrared spectroscopy (NIRS) can provide a more comprehensive picture of human brain function. Spectral entropy (SE) is a nonlinear method to summarize signal power irregularity over measured frequencies. SE was used as a joint measure to study whether spectral signal irregularity over a range of brain signal frequencies based on synchronous multimodal brain signals could provide new insights in the neural underpinnings of epileptiform activity. METHODS: Ten patients with focal drug-resistant epilepsy (DRE) and ten healthy controls (HC) were scanned with 10 Hz MREG sequence in combination with EEG, NIRS (measuring oxygenated, deoxygenated, and total hemoglobin: HbO, Hb, and HbT, respectively), and cardiorespiratory signals. After pre-processing, voxelwise SEMREG was estimated from MREG data. Different neurophysiological and physiological subfrequency band signals were further estimated from MREG, DC-EEG, and NIRS: fullband (0-5 Hz, FB), near FB (0.08-5 Hz, NFB), brain pulsations in very-low (0.009-0.08 Hz, VLFP), respiratory (0.12-0.4 Hz, RFP), and cardiac (0.7-1.6 Hz, CFP) frequency bands. Global dynamic fluctuations in MREG and NIRS were analyzed in windows of 2 min with 50% overlap. RESULTS: Right thalamus, cingulate gyrus, inferior frontal gyrus, and frontal pole showed significantly higher SEMREG in DRE patients compared to HC. In DRE patients, SE of cortical Hb was significantly reduced in FB (p = .045), NFB (p = .017), and CFP (p = .038), while both HbO and HbT were significantly reduced in RFP (p = .038, p = .045, respectively). Dynamic SE of HbT was reduced in DRE patients in RFP during minutes 2 to 6. Fitting to the frontal MREG and NIRS results, DRE patients showed a significant increase in SEEEG in FB in fronto-central and parieto-occipital regions, in VLFP in parieto-central region, accompanied with a significant decrease in RFP in frontal pole and parietal and occipital (O2, Oz) regions. CONCLUSION: This is the first study to show altered spectral entropy from synchronous MREG, EEG, and NIRS in DRE patients. Higher SEMREG in DRE patients in anterior cingulate gyrus together with SEEEG and SENIRS results in 0.12-0.4 Hz can be linked to altered parasympathetic function and respiratory pulsations in the brain. Higher SEMREG in thalamus in DRE patients is connected to disturbances in anatomical and functional connections in epilepsy. Findings suggest that spectral irregularity of both electrophysiological and hemodynamic signals are altered in specific way depending on the physiological frequency range.

Stretch- and H-reflexes of the lower leg during whole body cooling and local warming.

BACKGROUND: This study was undertaken to evaluate if possible changes in stretch- and H-reflexes could be related to the changes in the EMG activity of the cooled lower leg muscles observed during a stretch-shortening cycle exercise. METHODS: Eight subjects wearing shorts and jogging shoes were exposed once to 27 degrees C and twice to 10 degrees C for 60 min each. During the second exposure to 10 degrees C, the subject's lower legs were kept warm (10 degrees Clw) with electrical pillows. After the exposures Achilles tendon reflex (stretch reflex) was induced and the EMG activity of the triceps surae was measured. Immediately after reflex measurements the EMG activity of the triceps surae and tibialis anterior during a drop-jump (stretch-shortening cycle) was measured. After similar thermal exposures electrically induced H-reflex from the calf was measured. RESULTS: During the preactivity and stretch phases the EMG activity of the triceps surae increased after the exposure to 10 degrees C, whereas during the shortening phase it decreased. During the shortening phase cooling, on the contrary, increased the activity of tibialis surae anterior. These changes disappeared at 10 degrees Clw. At 10 degrees C the maximum EMG-amplitude of triceps surae during stretch reflex decreased (p<0.05), reflecting suppressed muscle spindle activity. Suppressed spindle activity causes the agonist to be unfacilitated and the antagonist muscle contraction to be uninhibited, which was seen in the present study as decreased agonist and increased antagonist EMG activity during the shortening phase at 10 degrees C. The Hmax/Mmax-ratio, H-reflex latency and amplitude increased at 10 degrees C (p<0.05), reflecting increased motoneuron pool excitability. This in part may explain the increased EMG activity during the preactivity and stretch phases. CONCLUSION: Cooling-induced increase in the excitability of the motoneuron pool and suppression of muscle spindle activity seem to be responsible of the EMG activity changes during the stretch-shortening cycle, consequently decreasing muscular performance.

Tibial nerve somatosensory evoked potentials during EEG suppression in sevoflurane anaesthesia.

OBJECTIVES AND METHODS: Cortical tibial nerve somatosensory evoked potentials (TSEPs) were recorded from 10 subjects in sevoflurane anaesthesia in order to study TSEP during EEG suppression. RESULTS: With a stimulation frequency less than one per second the major component was a positive wave which had maximal amplitude parietally ipsilaterally to stimulus and mean latency of 46.1 ms. It probably corresponds to the P40 wave. It was preceded by a widespread smaller positive wave, which corresponds to the subcortical P30 wave. In two patients a high amplitude negative wave, a couple of milliseconds before the positive wave, and maximal parietally contralateral to stimulus, was seen. All later waves were absent. CONCLUSION: The results are in agreement with our previous results from median nerve SEPs showing that the first cortical response from primary somatosensory cortex is enhanced, and later waves are suppressed. Hence, recording TSEPs during EEG suppression provides a way to record the activity of the primary somatosensory cortex accurately and rapidly due to the very good signal to noise ratio, so that even single responses to stimuli can be seen without averaging. Our results suggest that new cortical generators, which are not recordable awake, may be discovered in some patients.

Single-sweep cortical somatosensory evoked potentials: N20 and evoked bursts in sevoflurane anaesthesia.

Cortical evoked responses to median nerve stimulation were recorded from 21 subjects during sevoflurane anaesthesia at the level of burst suppression in EEG. The N20/P22 wave had the typical form of a negative wave postcentrally, and positive precentrally. The amplitude exceeded 4 microV in all patients, making it easily visible without averaging on the low-amplitude suppression. These results show that two kinds of somatosensory evoked potential can be studied without averaging during EEG suppression in deep anaesthesia. One is the localised N20/P22 wave, which is seen regularly during suppression after stimuli with intervals exceeding 1 s. The other is the burst, involving the whole cortex, which is not evoked by every stimulus. We suggest that somatosensory evoked potentials can be monitored during sevoflurane-induced EEG suppression, and often can be evaluated reliably from a couple of single sweeps with stimulation interval exceeding 1 s. The enhancement of early cortical components of SEP, their adaptation to repeated stimuli, and the disappearance of later polysynaptic components during EEG suppression, give new possibilities to study the generators of SEP and the different effects of anaesthetics.