3D regression neural network for the quantification of enlarged perivascular spaces in brain MRI

Enlarged perivascular spaces (EPVS) in the brain are an emerging imaging marker for cerebral small vessel disease, and have been shown to be related to increased risk of various neurological diseases, including stroke and dementia. Automated quantification of EPVS would greatly help to advance research into its etiology and its potential as a risk indicator of disease. We propose a convolutional network regression method to quantify the extent of EPVS in the basal ganglia from 3D brain MRI. We first segment the basal ganglia and subsequently apply a 3D convolutional regression network designed for small object detection within this region of interest. The network takes an image as input, and outputs a quantification score of EPVS. The network has significantly more convolution operations than pooling ones and no final activation, allowing it to span the space of real numbers. We validated our approach using a dataset of 2000 brain MRI scans scored visually. Experiments with varying sizes of training and test sets showed that a good performance can be achieved with a training set of only 200 scans. With a training set of 1000 scans, the intraclass correlation coefficient (ICC) between our scoring method and the expert's visual score was 0.74. Our method outperforms by a large margin - more than 0.10 - four more conventional automated approaches based on intensities, scale-invariant feature transform, and random forest. We show that the network learns the structures of interest and investigate the influence of hyper-parameters on the performance. We also evaluate the reproducibility of our network using a set of 60 subjects scanned twice (scan-rescan reproducibility). On this set our network achieves an ICC of 0.93, while the intrarater agreement reaches 0.80. Furthermore, the automated EPVS scoring correlates similarly to age as visual scoring

Enlarged perivascular spaces in brain MRI: Automated quantification in four regions

Enlarged perivascular spaces (PVS) are structural brain changes visible in MRI, are common in aging, and are considered a reflection of cerebral small vessel disease. As such, assessing the burden of PVS has promise as a brain imaging marker. Visual and manual scoring of PVS is a tedious and observer-dependent task. Automated methods would advance research into the etiology of PVS, could aid to assess what a “normal” burden is in aging, and could evaluate the potential of PVS as a biomarker of cerebral small vessel disease. In this work, we propose and evaluate an automated method to quantify PVS in the midbrain, hippocampi, basal ganglia and centrum semiovale. We also compare associations between (earlier established) determinants of PVS and visual PVS scores versus the automated PVS scores, to verify whether automated PVS scores could replace visual scoring of PVS in epidemiological and clinical studies. Our approach is a deep learning algorithm based on convolutional neural network regression, and is contingent on successful brain structure segmentation. In our work we used FreeSurfer segmentations. We trained and validated our method on T2-contrast MR images acquired from 2115 subjects participating in a population-based study. These scans were visually scored by an expert rater, who counted the number of PVS in each brain region. Agreement between visual and automated scores was found to be excellent for all four regions, with intraclass correlation coefficients (ICCs) between 0.75 and 0.88. These values were higher than the inter-observer agreement of visual scoring (ICCs between 0.62 and 0.80). Scan-rescan reproducibility was high (ICCs between 0.82 and 0.93). The association between 20 determinants of PVS, including aging, and the automated scores were similar to those between th

Инвазивный аспергиллез легких после трансплантации сердца

Objective: to assess the incidence, determine the peculiarities of the course of invasive pulmonary aspergillosis (IPA) and identify risk factors for IPA in heart transplant recipients.Materials and methods. From January 2010 to December 2019, 137 heart transplantations (HT) were performed: mean age 46 ± 14 years; male 102 (74%) and female 35 (26%). All patients received a three-component immunosuppressive therapy: calcineurin inhibitors, mycophenolate mofetil (MMF) and Glucocorticoid (GCs). Induction therapy consisted of Basiliximab (81%, n = 111) and antithymocyte immunoglobulin (15%, n = 20). A retrospective analysis of patients with identified post-HT invasive IPA was performed; risk factors for IPA were assessed. In patients with early IPA, the length of stay in the intensive care unit (ICU), the duration of mechanical ventilation, and the initial severity of the condition were studied. All patients with suspected pneumonia underwent bronchoscopy with examination of bronchoalveolar lavage (BAL) and chest computed tomography (chest CT scan).Results. During the follow-up, there were 58 episodes of pneumonia, of which 16 (28%) were IPA (age 33 to 64 years). All patients had a target level of immunosuppressive drugs concentration in blood; basiliximab was used as induction therapy in 15 of 16 patients. Half of the recipients developed IPA in the early post-HT period (less than 3 months after HT), in the rest (n = 8) – at a later date (3 months to 1 year after HT). The diagnosis was verified: 14 out of 16 patients showed an increase in the Aspergillus antigen positivity in the BAL to 7.2 (2.8 ± 1.6); chest CT scan revealed specific changes. In two patients, there were no diagnostic criteria for IPA, but the diagnosis was made based on the results of histological examination after resection of the left lower lobe of the lung. All patients received voriconazole therapy for 2 to 6 months, their immunosuppressive therapy was adjusted (tacrolimus and MMF dose adjustment) and their white blood cell count was monitored. Complete cure of the disease was achieved in 13 (81%) patients. Two patients died within 30 days after HT in the intensive care unit, one died from urogenital diseases caused by bacterial flora and leading to urosepsis, 4 months after IPA treatment was initiated. All patients had risk factors for IPA: taking immunosuppression, including GCs (n = 16), prolonged ICU stay (n = 14), inotropic support exceeding 2 days in the early post-transplant period (n = 10), cachexia during HT (n = 6), leukopenia (n = 9) and neutropenia (n = 14).Conclusion. In heart transplantat recipients, the incidence of IPA among respiratory tract infections is 28%. The risk of developing IPA was highest during the first year following HT. In the majority of recipients, the disease was detected at the early stages; diagnosis required surgical intervention in 12% of cases. A decrease in the risk of developing IPA was associated with correction of the following risk factors for this disease in all patients: volume of immunosuppressive therapy during the first year after transplantation and prevention of the development of neutropenia as a marker of infectious complications or immunosuppression overdose. Early diagnosis of IPA allowed for initiation of timely specific therapy in most recipients and achievement of a positive effect in 80% of them.Цель. Оценить частоту развития, определить особенности течения инвазивного аспергиллеза легких (АСП) и выявить факторы риска развития заболевания у реципиентов после трансплантации сердца (ТС).Материалы и методы. C января 2010-го по декабрь 2019 г. было выполнено 137 ТС: средний возраст 46 ± 14 лет; мужчин – 102 (74%), женщин – 35 (26%). Все пациенты получали трехкомпонентную иммуносупрессивную терапию: ингибиторы кальциневрина, микофенолата мофетил (ММФ) и глюкокортикостероиды (ГКС). Индукционная терапия была представлена базиликсимабом (81%, n = 111) и антитимоцитарным иммуноглобулином (15%, n = 20). Проведен ретроспективный анализ пациентов с выявленным инвазивным АСП, перенесенным после ТС, оценены факторы риска развития АСП. У пациентов с ранним АСП изучены длительность нахождения в отделении реанимации (ОР) и продолжительность ИВЛ, исходная тяжесть состояния. Всем пациентам с подозрением на пневмонию проводились бронхоскопия с исследованием бронхоальвеолярного лаважа (БАЛ) и компьютерная томография грудной клетки (КТ ОГК).Результаты. За время наблюдения было зарегистрировано 58 эпизодов пневмоний, из них 16 (28%) – АСП (возраст от 33 до 64 лет). У всех пациентов был целевой уровень концентрации иммуносупрессивных препаратов в крови, у 15 из 16 пациентов в качестве индукционной терапии был применен базиликсимаб. У половины реципиентов АСП развился в ранние сроки после ТС (менее 3 месяцев после ТС), у остальных (n = 8) – в поздние сроки (3 месяца – 1 год после ТС). Диагноз был верифицирован: у 14 из 16 пациентов наблюдалось повышение коэффициента позитивности антиген Aspergillus в БАЛ до 7,2 (2,8 ± 1,6), имели место специфические изменения по КТ ОГК. У двух пациентов диагностические критерии АСП отсутствовали, но диагноз был поставлен по результатам гистологического исследования после резекции нижней доли левого легкого. Всем пациентам проводилась терапия вориконазолом продолжительностью от 2 до 6 месяцев, коррекция иммуносупрессивной терапии (коррекция дозы такролимуса и ММФ) и контроль уровня лейкоцитов в динамике. Полное излечение заболевания было достигнуто у 13 (81%) пациентов. Двое больных умерли в течение 30 дней после ТС в отделении реанимации, один – от заболеваний мочеполовой системы, вызванных бактериальной флорой и приведших к развитию уросепсиса, через 4 месяца после начала лечения АСП. У всех пациентов имели место факторы риска развития АСП: прием иммуносупрессии, в том числе ГКС (n = 16), длительное пребывание в ОР (n = 14), инотропная поддержка более 2 суток в раннем посттрансплантационном периоде (n = 10), кахексия на момент ТС (n = 6), лейкопения (n = 9) и нейтропения (n = 14).Заключение. У пациентов после ТС встречаемость АСП среди инфекций дыхательных путей составляет 28%. Наиболее высоким риск развития АСП был в течение первого года после ТС. У большинства реципиентов заболевание было выявлено на начальных стадиях, в 12% случаев для диагностики потребовалось проведение оперативного вмешательства. Снижение риска развития АСП было ассоциировано с коррекцией следующих факторов риска этого заболевания у всех пациентов: объем иммуносупрессивной терапии в течение первого года после трансплантации и предотвращение развития нейтропении как маркера инфекционных осложнений или переизбытка иммуносупрессии. Ранняя диагностика АСП позволила у большинства реципиентов начать своевременную специфическую терапию и добиться положительного эффекта у 80% из них

Mitosis detection in intestinal crypt images with hough forest and conditional random fields.

Intestinal enteroendocrine cells secrete hormones that are vital for the regulation of glucose metabolism but their differentiation from intestinal stem cells is not fully understood. Asymmetric stem cell divisions have been linked to intestinal stem cell homeostasis and secretory fate commitment. We monitored cell divisions using 4D live cell imaging of cultured intestinal crypts to characterize division modes by means of measurable features such as orientation or shape. A statistical analysis of these measurements requires annotation of mitosis events, which is currently a tedious and time-consuming task that has to be performed manually. To assist data processing, we developed a learning based method to automatically detect mitosis events. The method contains a dual-phase framework for joint detection of dividing cells (mothers) and their progeny (daughters). In the first phase we detect mother and daughters independently using Hough Forest whilst in the second phase we associate mother and daughters by modelling their joint probability as Conditional Random Field (CRF). The method has been evaluated on 32 movies and has achieved an AUC of 72%, which can be used in conjunction with manual correction and dramatically speed up the processing pipeline

The effect of aerobic exercise on muscle tissue in patients with severe heart failure and normal body weight

Aim. To assess the response of skeletal muscle and myocardium to original aerobic exercise (AE) program in patients with heart failure (HF) with reduced ejection fraction (HFrEF); to assess morphometric changes in skeletal muscle fiber after AE.Material and methods. The study included 100 patients with class III HFrEF (age — 52±5,2 years; body mass index (BMI) — 23,5±2,8 kg/m2). At baseline and after 6 months of AE, an echocardiogram, peak oxygen uptake (VO2peak), exercise tolerance and quality of life (QOL) were evaluated. Lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) activity were evaluated in biopsy material of lower leg muscles.Results. After 6 months of AE, the left ventricular ejection fraction (LVEF) increased by 10,5±2,3%, QOL — by 24,8±3,5 points, exercise tolerance — by 9,7±0,5 points, VO2peak — by 5,2±0,5 ml/min/kg (p1,2,3,4< 0,05). In 6 patients, the diameter of muscle fiber decreased slightly. The activity of ALP (initially — 0,33±0,09 D) increased by 24,2% (p< 0,05); LDH in glycolytic fibers was initially 0,213±0,08 D, in oxidative fibers — 0,083±0,04, and after 6 months of AE, decreased by 24,4% and 6,0%, respectively (p1 <0,05, p2 >0,05). A positive relationship was found between the dynamics of HF class and fiber diameter (r=0,4, p=0,05); an increase in сardiopulmonary exercise test was associated with ALP activity (r=0,5, p=0,05).Conclusion. 1. Dosed aerobic exercise in patients with stable class III HFrEF, normal BMI, based on reaching the lactate threshold, had a positive effect on LVEF, QOL, exercise tolerance and VO2peak. 2. With exercise training, a decrease in fiber diameter and LDH activity in both oxidative and glycolytic fibers, an increase in ALP activity were revealed. 3. The functional relationship between the increase in exercise tolerance and ALP content in muscle tissue was revealed

Electrophysiological characteristics of telocytes of the atrioventricular note and sinoatrial node perifocal area in humans and pigs

Little is known about the electrophysiological characteristics of telocytes found in the working myocardium and sinoatrial node (SAN). Telocyte expres -sion of HCN4 suggests the ability to generate pacemaker potentials. To prove the impulse conduction, the presence of voltage-gated sodium channels is required. It is assumed that telocytes are also located in the atrioventricular node (AVN).Aim. Morphological and electrophysiological study of AVN and SAN telocytes.Material and methods. Fragments of the right atrium, AVN of 7 hearts of recipients and 3 hearts of pigs were taken, respectively, during heart transplantation and after the experiment. Isolation of telocyte cultures, histological, immunohis tochemical tests with anti-CD117, anti-NaV1.5 (SCN5A), anti-CD34 antibodies, intravital confocal laser microscopy were carried out. The patch-clamp technique was used.Results. In AVN cultures, CD117+ cells with long processes were found. There was a potassium current with a density of 700 pA/pF during membrane depolarization up to +90 mW in humans and pigs using the patch-clamp technique. Calcium oscillations with a period of about 200 seconds in a pig with an increase in calcium concentration. In elongated cells located between cardiomyocytes and among the fibrous tissue of SAN perifocal zone, the co-expression of anti-NaV1.5 and anti-CD34 antibodies was revealed.Conclusion. In AVN, telocytes were found, in whose cultures potassium current and calcium oscillations were determined. SCN5A sodium channels were found in telocytes of the perifocal area of human SAN. This fact indicates the ability of cells to conduct an electrical impulse