A Data-Driven Approach for Estimating Temperature Variations Based on B-mode Ultrasound Images and Changes in Backscattered Energy.

Thermal treatments that use ultrasound devices as a tool have as a key point the temperature control to be applied in a specific region of the patient's body. This kind of procedure requires caution because the wrong regulation can either limit the treatment or aggravate an existing injury. Therefore, determining the temperature in a region of interest in real-time is a subject of high interest. Although this is still an open problem, in the field of ultrasound analysis, the use of machine learning as a tool for both imaging and automated diagnostics are application trends. In this work, a data-driven approach is proposed to address the problem of estimating the temperature in regions of a B-mode ultrasound image as a supervised learning problem. The proposal consists in presenting a novel data modeling for the problem that includes information retrieved from conventional B-mode ultrasound images and a parametric image built based on changes in backscattered energy (CBE). Then, we compare the performance of classic models in the literature. The computational results presented that, in a simulated scenario, the proposed approach that a Gradient Boosting model would be able to estimate the temperature with a mean absolute error of around 0.5°C, which is acceptable in practical environments both in physiotherapic treatments and high intensity focused ultrasound (HIFU).

Relationship between intervention dosage and success of resource connections in a social needs intervention.

OBJECTIVES: Social needs interventions in medical settings aim to mitigate the effects of adverse social circumstances on health outcomes by connecting vulnerable patients with resources. This study examined the relationship between intervention dosage and the success of resource connections using data from a social needs intervention in multiple clinical settings across the US. STUDY DESIGN: The intervention uses a case management approach to connect patients with unmet needs to resources and services in the community. Intervention dosage was conceptualized as the number of contacts between the navigator and the patient, categorized as direct contact (phone vs. in person) and indirect contact (initiated by the navigator vs. patient). Success of the intervention was conceptualized as 'none,' 'partial,' or 'optimal' for each patient, based on the number of social needs the resource connections addressed. METHODS: Administrative data were extracted for 38,404 unique patients who screened positive for unmet resource needs between 2012 and 2017. Owing to the large sample size, statistical corrections were made to reduce type I error. RESULTS: Multinomial logistic regression analyses showed that higher intervention dosage was related to greater success of resource connections, after adjusting for the patient and site characteristics, and the number of needs (odds ratios ranged from 1.62 to 2.89). In-person contact, although received by only 25% of the patients, was associated with the highest probability of optimal success. CONCLUSIONS: This study demonstrates a feasible way to conceptualize an intervention dose for a social needs intervention that uses a case management approach and has implications for how intervention delivery may improve success of resource connections.

Durability study of a gellan gum-based tissue-mimicking phantom for ultrasonic thermal therapy.

Stability and duration of ultrasonic phantoms are still subjects of research. This work presents a tissue-mimicking material (TMM) to evaluate high-intensity therapeutic ultrasound (HITU) devices, composed of gellan gum (matrix), microparticles (scatterers), and chemicals. The ultrasonic velocity and attenuation coefficient were characterized as a function of temperature (range 20 °C-85 °C). The nonlinear parameter B/A was determined by the finite amplitude insertion substitution (FAIS) method, and the shear modulus was determined by a transient elastography technique. The thermal conductivity and specific heat were determined by the line source method. The attenuation was stable for 60 days, and in an almost linear frequency dependence (0.51f0.96 dB cm-1), at 20 °C (1-10 MHz). All other evaluated physical parameters are also close to typical soft tissue values. Longitudinal ultrasonic velocities were between 1.49 and 1.75 mm µs-1, the B/A parameter was 7.8 at 30 °C, and Young's modulus was 23.4 kPa. The thermal conductivity and specific heat values were 0.7 W(m K)-1 and 4.7 kJ(kg K)-1, respectively. Consistent temperature increases and thermal doses occurred under identical HITU exposures. Low cost, longevity, thermal stability, and thermal repeatability make TMM an excellent material for ultrasonic thermal applications. The TMM developed has the potential to assess the efficacy of hyperthermia devices and could be used to adjust the ultrasonic emission of HITU devices.

Oral and topical boswellic acid attenuates mouse osteoarthritis.

OBJECTIVE: Boswellic acid is a plant-derived molecule with putative anti-inflammatory effects. This study was performed to determine whether oral or topical administration of boswellic acid can attenuate joint damage in a mouse model of osteoarthritis (OA). METHODS: Levels of boswellic acid were measured in the blood and synovium of mice treated with oral or topical boswellic acid. OA was generated by surgical destabilization of the medial meniscus (DMM). Therapy with oral or topical boswellic acid was initiated one day after surgery and continued for 12 weeks, when knees were harvested and scored histologically for degree of cartilage loss, osteophyte formation, and synovitis. Microdissected OA synovium was stimulated with IL-1ß or lipopolysaccharide (LPS) in the presence or absence of boswellic acid and cytokine production by quantitative polymerase chain reaction (PCR) or multiplex enzyme linked immunoabsorbant assay (ELISA). RESULTS: Topical treatment resulted in synovial concentrations of boswellic acid 2-6-fold higher than that measured in plasma. Cartilage loss was significantly reduced in mice treated with oral or topical boswellic acid compared with vehicle control (P < 0.01 for both oral and topical therapies). Likewise, treatment with either oral boswellic acid or boswellic acid ointment reduced of synovitis (P = 0.006 and 0.025, respectively) and osteophyte formation (P = 0.009 and 0.030, respectively). In vitro, boswellic acid was able to inhibit IL-1ß and TLR4 mediated induction of several inflammatory mediators from OA synovial explant tissue. CONCLUSIONS: Significant synovial concentration and therapeutic efficacy can be achieved with topical boswellic acid treatment. These findings suggest that boswellic acid has potential as a disease-modifying agent in OA.

Homozygous and compound heterozygous mutations in the ATP6V1B1 gene in patients with renal tubular acidosis and sensorineural hearing loss.

Distal renal tubular acidosis (dRTA) is characterized by the inability to excrete acid in the renal collecting ducts resulting in inappropriately alkaline urine and hyperchloremic (normal anion gap) metabolic acidosis in the context of a normal (or near-normal) glomerular filtration rate. Inborn dRTA can be due to autosomal dominant or recessive gene defects. Clinical symptoms vary from mild acidosis, incidental detection of kidney stones or renal tract calcification to severe findings such as failure to thrive, severe metabolic acidosis, and nephrocalcinosis. The majority of patients with recessive dRTA present with sensorineural hearing loss (SNHL). Few cases with abnormal widening of the vestibular aqueduct have been described with dRTA. Mutations in three different genes have been identified, namely SLC4A1, ATP6V1B1, and ATP6V0A4. Patients with mutations in the ATP6V1B1 proton pump subunit develop dRTA and in most of the cases sensorineural hearing loss early in childhood. We present two patients from two different and non-consanguineous families with dRTA and SNHL. Direct sequencing of the ATP6V1B1 gene revealed that one patient harbors two homozygous mutations and the other one is a compound heterozygous. To our knowledge, this is the first case in the literature describing homozygosity in the same dRTA gene on both alleles.

The AE4 transporter mediates kidney acid-base sensing.

The kidney plays a key role in the correction of systemic acid-base imbalances. Central for this regulation are the intercalated cells in the distal nephron, which secrete acid or base into the urine. How these cells sense acid-base disturbances is a long-standing question. Intercalated cells exclusively express the Na+-dependent Cl-/HCO3- exchanger AE4 (Slc4a9). Here we show that AE4-deficient mice exhibit a major dysregulation of acid-base balance. By combining molecular, imaging, biochemical and integrative approaches, we demonstrate that AE4-deficient mice are unable to sense and appropriately correct metabolic alkalosis and acidosis. Mechanistically, a lack of adaptive base secretion via the Cl-/HCO3- exchanger pendrin (Slc26a4) is the key cellular cause of this derailment. Our findings identify AE4 as an essential part of the renal sensing mechanism for changes in acid-base status.

Quadratic versus linear models to estimate the mean scattering spacing as a function of temperature in ex-vivo tissue.

Previous works have shown the feasibility of temperature estimation during ultrasonic therapy using pulse-echo diagnostic ultrasound. These methods are based on the measurement of thermally induced changes in backscattered RF echoes due to thermal expansion and changes in ultrasonic velocity. They assume a joint contribution of these two parameters and a linear dependence with temperature. In this work, the contributions of velocity changes and thermal expansion to the evolution of the mean scatterer spacing of ex vivo bovine skeletal muscle tissue samples were decoupled. This was achieved by employing an experimental setup which allows measuring the absolute velocity value, using the through-transmission technique in a direct transmission configuration. The mean-scatterer spacing was estimated from spectral analysis of the backscattered signals obtained in pulse-echo mode. We propose a quadratic model of the thermal expansion coefficient to fit the evolution of the mean-scatterer spacing with temperature. The temperature increase estimated by the linear model, in the range of 29.5-47 °C, presents a percentage error (mean square error) of 11 %, while for the quadratic model the error is 4.8 %.

Assessing the combined performance of texture and morphological parameters in distinguishing breast tumors in ultrasound images.

PURPOSE: This work aims to investigate the combination of morphological and texture parameters in distinguishing between malignant and benign breast tumors in ultrasound images. METHODS: Linear discriminant analysis was applied to sets of up to five parameters, and then the performances were assessed using the area A(z) (± standard error) under the receiver operator characteristic curve, accuracy (Ac), sensitivity (Se), specificity (Sp), positive predictive value, and negative predictive value. RESULTS: The most relevant individual parameter was the normalized residual value (nrv), calculated from the convex polygon technique. The best performance among all studied combinations was achieved by two morphological and three texture parameters (nrv, con, std, R, and asm(i)), which correctly distinguished nearly 85% of the breast tumors. CONCLUSIONS: This result indicates that the combination of morphological and texture parameters may be useful to assist physicians in the diagnostic process, especially if it is associated with an automatic classification tool.

Method for estimating average grey-level's measurement uncertainty from ultrasound images for non-invasive estimation of temperature in different tissue types.

The objective of this work is to assess, on metrological basis, the average grey-levels (AVGL) calculated from B-Mode images for estimating temperature variations non-invasively in different kinds of tissues. Thermal medicine includes several thermal therapies, being hyperthermia the most noted and well known. Recently, efforts have been made to understand the benefits of ultrasound hyperthermia at mild temperature levels, i.e., between 39 °C and 41 °C. Moreover, the best practices on ultrasound bio-effects research have been encouraged by recommending that temperature rise in the region of interest should be measured even when a thermal mechanism is not being tested. In this work, the average grey-levels (AVGL) calculated from B-Mode images were assessed for non-invasive temperature estimation in a porcine tissue sample containing two different tissue types, fat and muscle, with temperature varying from 35 °C to 41 °C. The sample was continuously imaged with an ultrasound scanner, and simultaneously the temperature was measured. The achieved results were assessed under the light of the measurement uncertainty in order to allow comparability among different ultrasound thermometry methods. The highest expanded uncertainty of estimating temperature variation using AVGL was determined as 0.68 °C.

Evidence for endomycorrhizae in pennsylvanian age plant fossils.

Fossil fungal chlamydospores from the tissues of a number of Pennsylvanian age fossil plants are described. Features such as size, shape, wall organization, and the structure of the subtending hyphal stalk suggest affinities with the modern endomycorrhizal fungus Glomus.

Gravity field of venus: a preliminary analysis.

The line-of-sight gravity field for Venus has been mapped by tracking the Pioneer Venus spacecraft in the vicinity of periapsis for a 45 degrees swath of longitude eastward of 294 degrees . There are consistent and systematic variations in the gravity signature from orbit to orbit, attesting to the reality of observed anomalies. Orbit 93 passes over a large positive topographic feature, the "northern plateau," for which there is no corresponding gravity signature. If this region has no isostatic compensation, the gravity signal would exceed the noise level by a factor of 7. The results of simulation modeling indicate that the northern plateau must be compensated at depths of about 100 kilometers or less. The long-wavelength anomalies seen in the Venus gravity data have been Fourier-decomposed along the orbital tracks and compared to analogous spectra for Earth. The gross power in the two mean spectra is approximately, the same, but systematic variations among the harmonics suggest differences in dynamic processes or lithospheric behavior, or both, for the two planets.

The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis.

Intestinal fibrosis and stenosis are common complications of Crohn's disease [CD], frequently requiring surgery. Anti-inflammatory strategies can only partially prevent fibrosis; hence, anti-fibrotic therapies remain an unmet clinical need. Oxysterols are oxidised cholesterol derivatives with important roles in various biological processes. The enzyme cholesterol 25-hydroxylase [CH25H] converts cholesterol to 25-hydroxycholesterol [25-HC], which modulates immune responses and oxidative stress. In human intestinal samples from CD patients, we found a strong correlation of CH25H mRNA expression with the expression of fibrosis markers. We demonstrate reduced intestinal fibrosis in mice deficient for the CH25H enzyme, using the sodium dextran sulphate [DSS]-induced chronic colitis model. Additionally, using a heterotopic transplantation model of intestinal fibrosis, we demonstrate reduced collagen deposition and lower concentrations of hydroxyproline in CH25H knockouts. In the heterotopic transplant model, CH25H was expressed in fibroblasts. Taken together, our findings indicate an involvement of oxysterol synthesis in the pathogenesis of intestinal fibrosis.

Cloning and functional characterization of human SMCT2 (SLC5A12) and expression pattern of the transporter in kidney.

Recently, we cloned two Na(+)-coupled lactate transporters from mouse kidney, a high-affinity transporter (SMCT1 or slc5a8) and a low-affinity transporter (SMCT2 or slc5a12). Here we report on the cloning and functional characterization of human SMCT2 (SLC5A12) and compare the immunolocalization patterns of slc5a12 and slc5a8 in mouse kidney. The human SMCT2 cDNA codes for a protein consisting of 618 amino acids. When expressed in mammalian cells or Xenopus oocytes, human SMCT2 mediates Na(+) -coupled transport of lactate, pyruvate and nicotinate. The affinities of the transporter for these substrates are lower than those reported for human SMCT1. Several non-steroidal anti-inflammatory drugs inhibit human SMCT2-mediated nicotinate transport, suggesting that NSAIDs interact with the transporter as they do with human SMCT1. Immunofluorescence microscopy of mouse kidney sections with an antibody specific for SMCT2 shows that the transporter is expressed predominantly in the cortex. Similar studies with an anti-SMCT1 antibody demonstrate that SMCT1 is also expressed mostly in the cortex. Dual-labeling of SMCT1 and SMCT2 with 4F2hc (CD98), a marker for basolateral membrane of proximal tubular cells in the S1 and S2 segments of the nephron, shows that both SMCT1 and SMCT2 are expressed in the apical membrane of the tubular cells. These studies also show that while SMCT2 is broadly expressed along the entire length of the proximal tubule (S1/S2/S3 segments), the expression of SMCT1 is mostly limited to the S3 segment. These studies suggest that the low-affinity transporter SMCT2 initiates lactate absorption in the early parts of the proximal tubule followed by the participation of the high-affinity transporter SMCT1 in the latter parts of the proximal tubule.

When proton pumps go sour: Urinary acidification and kidney stones.

H(+)-ATPases mediate urinary acidification along the collecting duct, and mutations in their B1 and a4 subunits result in distal renal tubular acidosis. The pathomechanisms by which these mutations affect pump activity are only poorly understood. Common polymorphisms may impair pump activity and may link the pump to a higher risk for alkaline urine and the development of kidney stones.

Neuro-genetic non-invasive temperature estimation: intensity and spatial prediction.

OBJECTIVES: The existence of proper non-invasive temperature estimators is an essential aspect when thermal therapy applications are envisaged. These estimators must be good predictors to enable temperature estimation at different operational situations, providing better control of the therapeutic instrumentation. In this work, radial basis functions artificial neural networks were constructed to access temperature evolution on an ultrasound insonated medium. METHODS: The employed models were radial basis functions neural networks with external dynamics induced by their inputs. Both the most suited set of model inputs and number of neurons in the network were found using the multi-objective genetic algorithm. The neural models were validated in two situations: the operating ones, as used in the construction of the network; and in 11 unseen situations. The new data addressed two new spatial locations and a new intensity level, assessing the intensity and space prediction capacity of the proposed model. RESULTS: Good performance was obtained during the validation process both in terms of the spatial points considered and whenever the new intensity level was within the range of applied intensities. A maximum absolute error of 0.5 degrees C+/-10% (0.5 degrees C is the gold-standard threshold in hyperthermia/diathermia) was attained with low computationally complex models. CONCLUSION: The results confirm that the proposed neuro-genetic approach enables foreseeing temperature propagation, in connection to intensity and space parameters, thus enabling the assessment of different operating situations with proper temperature resolution.

Ex vivo determined experimental correction factor for the ultrasonic source term in the bioheat equation.

The objective of this work is to propose an effective absorption coefficient (αeffec) as an empirical correction factor in the source term of the bioheat equation. The temperature rise in biological tissue due to ultrasound insonification is produced by energy absorption. Usually, the ultrasonic absorption coefficient (αA) is used as a source term in the bioheat equation to quantify the temperature rise, and the effect of scattering is disregarded. The coefficient αeffec includes the scattering contribution as an additional absorption term and should allow us to make a better estimation of the thermal dose (TD), which is important for clinical applications. We simulated the bioheat equation with the source term considering αA or αeffec, and with heating provided by therapeutic ultrasound (1MHz, 2.0Wcm-2) for about 5.5min (temperature range 36-46°C). Experimental data were obtained in similar heating conditions for a bovine muscle tissue (ex vivo) and temperature curves were measured for depths 7, 30, 35, 40 and 45mm. The TD values from the experimental temperature curves at each depth were compared with the numerical solution of the bioheat equation with the classical and corrected source terms. The highest percentual difference between simulated and experimental TD was 42.5% when assuming the classical αA, and 8.7% for the corrected αeffec. The results show that the effective absorption coefficient is a feasible parameter to improve the classical bioheat transfer model, especially for depths larger than the mean free propagation path.

Complexity curve and grey level co-occurrence matrix in the texture evaluation of breast tumor on ultrasound images.

This work aims at investigating texture parameters in distinguishing malign and benign breast tumors on ultrasound images. A rectangular region of interest (ROI) containing the tumor and its neighboring was defined for each image. Five parameters were extracted from the complexity curve (CC) of the ROI. Another five parameters were calculated from the grey-level co-occurrence matrix (GLCM) also for the ROI. The same was carried out for internal tumor region, hence, totaling 20 parameters. The linear discriminant analysis was applied to sets of up to five parameters and then the performances were assessed. The most relevant individual parameters were the contrast (con) (from the GLCM over the ROI) and the maximum value (mvi) from the CC just for the tumor internal region). When they were taken together, a correct classification slightly over 80% of the breast tumors was achieved. The highest performance (accuracy=84.2%, sensitivity=87.0%, and specificity=78.8%) was obtained with mvi, con, the standard deviation of the pixel pairs and the entropy, both for GLCM, and the internal region contrast also from GLCM. Parameters extracted from the internal region generally performed better and were more significant than those from the ROI. Moreover, parameters calculated only from CC or GLCM resulted in no statistically significant performance difference. These findings suggest that the texture parameters can be useful to help radiologist in distinguishing between benign or malign breast tumors on ultrasound images.