Feasibility of brain age predictions from clinical T1-weighted MRIs

An individual's brain predicted age minus chronological age (brain-PAD) obtained from MRIs could become a biomarker of disease in research studies. However, brain age reports from clinical MRIs are scant despite the rich clinical information hospitals provide. Since clinical MRI protocols are meant for specific clinical purposes, performance of brain age predictions on clinical data need to be tested. We explored the feasibility of using DeepBrainNet, a deep network previously trained on research-oriented MRIs, to predict the brain ages of 840 patients who visited 15 facilities of a health system in Florida. Anticipating a strong prediction bias in our clinical sample, we characterized it to propose a covariate model in group-level regressions of brain-PAD (recommended to avoid Type I, II errors), and tested its generalizability, a requirement for meaningful brain age predictions in new single clinical cases. The best bias-related covariate model was scanner-independent and linear in age, while the best method to estimate bias-free brain ages was the inverse of a scanner-independent and quadratic in brain age function. We demonstrated the feasibility to detect sex-related differences in brain-PAD using group-level regression accounting for the selected covariate model. These differences were preserved after bias correction. The Mean-Average Error (MAE) of the predictions in independent data was ∼8 years, 2-3 years greater than reports for research-oriented MRIs using DeepBrainNet, whereas an R2 (assuming no bias) was 0.33 and 0.76 for the uncorrected and corrected brain ages, respectively. DeepBrainNet on clinical populations seems feasible, but more accurate algorithms or transfer-learning retraining is needed

Toward MR protocol-agnostic, unbiased brain age predicted from clinical-grade MRIs

The difference between the estimated brain age and the chronological age ('brain-PAD') could become a clinical biomarker. However, most brain age models were developed for research-grade high-resolution T1-weighted MRIs, limiting their applicability to clinical-grade MRIs from various protocols. We adopted a dual-transfer learning strategy to develop a model agnostic to modality, resolution, or slice orientation. We retrained a convolutional neural network (CNN) using 6281 clinical MRIs from 1559 patients, among 7 modalities and 8 scanner models. The CNN was trained to estimate brain age from synthetic research-grade magnetization-prepared rapid gradient-echo MRIs (MPRAGEs) generated by a 'super-resolution' method. The model failed with T2-weighted Gradient-Echo MRIs. The mean absolute error (MAE) was 5.86-8.59 years across the other modalities, still higher than for research-grade MRIs, but comparable between actual and synthetic MPRAGEs for some modalities. We modeled the "regression bias" in brain age, for its correction is crucial for providing unbiased summary statistics of brain age or for personalized brain age-based biomarkers. The bias model was generalizable as its correction eliminated any correlation between brain-PAD and chronological age in new samples. Brain-PAD was reliable across modalities. We demonstrate the feasibility of brain age predictions from arbitrary clinical-grade MRIs, thereby contributing to personalized medicine

Tumor en la enfermedad renal poliquística. Presentación de un caso / Tumors in polycystic kidney disease. A case report

El carcinoma de la célula renal es encontrado en muy poca probabilidad en la enfermedad renal poliquística autosómica dominante. El objetivo de este trabajo es presentar un caso tratado por insuficiencia renal crónica progresiva en el curso de una enfermedad renal poliquística autosómica dominante, el cual sufre graves complicaciones y es intervenido quirúrgicamente, encontrándose en el acto quirúrgico la asociación de un tumor con una enfermedad renal poliquística autosómica dominante. La intervención quirúrgica se realizó en el servicio de Urología del Hospital General Docente "Abel Santamaría Cuadrado" en junio de 2009. La paciente acude a consulta por un cuadro hemorrágico urinario y dolor lumbar gravativo, se constata las mucosas: hipocoloreadas y húmedas, y en el aparato cardiovascular: ruidos cardiacos y taquicardicos, frecuencia cardiaca: 110 x minuto y TA: 190/110 mmHg, se ingresa al paciente e indica tratamiento sintomático además de estudios hematológicos y radiológicos: Hematocrito ( 0,40 L/L), Glicemia (4,5 mmol-L), Conteo de plaquetas ( 18 / 109 /L), Creatinina (110 mmol/L), Electrocardiograma (Taquicardia sinusal) y orina (Hematuria Macroscópica). Ecografía abdominal: Riñón izquierdo aumentado de tamaño con múltiples imágenes eco lúcidas, el riñón derecho muy aumentado de tamaño con imágenes eco lúcidas hacia polo superior, deformidad de la parte media y polo inferior del mismo, por tumor ecogénico de 140 x 100 mm., Tomografía axial computarizada: Masas hipodensas regulares en riñón izquierdo, masas hipodensas en riñón derecho, masa tumoral a nivel del mismo. Se realiza nefrectomía derecha confirmando el diagnóstico. La evolución fue satisfactoria con egreso a los 7 días de la intervención.Palabras clave: Enfermedad renal poliquística, autosómico dominante.ABSTRACTRenal cell carcinoma is rarely found in the autosomal dominant polycystic kidney disease (ADPKD). The objective of this work is to present a case treated by progressive chronic renal failure in the course of ADPKD, whose patient suffers from severe complications, finding a tumor associated to ADPKD during the surgery. The surgery was performed in the service of urology at "Abel Santamaria Cuadrado" University Hospital in June 2009. The patient attended to the hospital presenting a hemorrhagic urinary and lumbar gravitational pain picture. The mucosae were hypocolored and wet. Cardiovascular system presented: cardiac sounds and tachycardia, cardiac rate: 110 x minute and BP: 190/110 mmHg. The patient was hospitalized and the treatment was indicated, the hematologic and radiographic studies showed: hematocrit (0, 40 L/L), blood glucose (4, 5 mmol-L), platelet counts (18 / 109 /L), creatinine (110 mmol/L). The electrocardiogram showed a sinus tachycardia and in the urinalysis a macroscopic hematuria was observed. Detecting in the abdominal echography an enlargement in the left kidney with multiple echolucid images and the right kidney was enlarged with echolucid images towards the superior pole with a deformity in the middle part and in the inferior pole due to an echogenic tumor of 140x100mm. The CAT scan showed: regular hypodense masses in left kidney as well as hypodense masses in the right kidney and a tumoral mass in its level. The right nephrectomy was performed confirming the diagnosis. The evolution was satisfactory and the patient was discharged from the hospital at 7 days after the surgical intervention.Key words: Polycystic kidney disease; autosomal dominan

Tumor en la enfermedad renal poliquística. Presentación de un caso / Tumors in polycystic kidney disease. A case report

El carcinoma de la célula renal es encontrado en muy poca probabilidad en la enfermedad renal poliquística autosómica dominante. El objetivo de este trabajo es presentar un caso tratado por insuficiencia renal crónica progresiva en el curso de una enfermedad renal poliquística autosómica dominante, el cual sufre graves complicaciones y es intervenido quirúrgicamente, encontrándose en el acto quirúrgico la asociación de un tumor con una enfermedad renal poliquística autosómica dominante. La intervención quirúrgica se realizó en el servicio de Urología del Hospital General Docente "Abel Santamaría Cuadrado" en junio de 2009. La paciente acude a consulta por un cuadro hemorrágico urinario y dolor lumbar gravativo, se constata las mucosas: hipocoloreadas y húmedas, y en el aparato cardiovascular: ruidos cardiacos y taquicardicos, frecuencia cardiaca: 110 x minuto y TA: 190/110 mmHg, se ingresa al paciente e indica tratamiento sintomático además de estudios hematológicos y radiológicos: Hematocrito ( 0,40 L/L), Glicemia (4,5 mmol-L), Conteo de plaquetas ( 18 / 109 /L), Creatinina (110 mmol/L), Electrocardiograma (Taquicardia sinusal) y orina (Hematuria Macroscópica). Ecografía abdominal: Riñón izquierdo aumentado de tamaño con múltiples imágenes eco lúcidas, el riñón derecho muy aumentado de tamaño con imágenes eco lúcidas hacia polo superior, deformidad de la parte media y polo inferior del mismo, por tumor ecogénico de 140 x 100 mm., Tomografía axial computarizada: Masas hipodensas regulares en riñón izquierdo, masas hipodensas en riñón derecho, masa tumoral a nivel del mismo. Se realiza nefrectomía derecha confirmando el diagnóstico. La evolución fue satisfactoria con egreso a los 7 días de la intervención.Palabras clave: Enfermedad renal poliquística, autosómico dominante.ABSTRACTRenal cell carcinoma is rarely found in the autosomal dominant polycystic kidney disease (ADPKD). The objective of this work is to present a case treated by progressive chronic renal failure in the course of ADPKD, whose patient suffers from severe complications, finding a tumor associated to ADPKD during the surgery. The surgery was performed in the service of urology at "Abel Santamaria Cuadrado" University Hospital in June 2009. The patient attended to the hospital presenting a hemorrhagic urinary and lumbar gravitational pain picture. The mucosae were hypocolored and wet. Cardiovascular system presented: cardiac sounds and tachycardia, cardiac rate: 110 x minute and BP: 190/110 mmHg. The patient was hospitalized and the treatment was indicated, the hematologic and radiographic studies showed: hematocrit (0, 40 L/L), blood glucose (4, 5 mmol-L), platelet counts (18 / 109 /L), creatinine (110 mmol/L). The electrocardiogram showed a sinus tachycardia and in the urinalysis a macroscopic hematuria was observed. Detecting in the abdominal echography an enlargement in the left kidney with multiple echolucid images and the right kidney was enlarged with echolucid images towards the superior pole with a deformity in the middle part and in the inferior pole due to an echogenic tumor of 140x100mm. The CAT scan showed: regular hypodense masses in left kidney as well as hypodense masses in the right kidney and a tumoral mass in its level. The right nephrectomy was performed confirming the diagnosis. The evolution was satisfactory and the patient was discharged from the hospital at 7 days after the surgical intervention.Key words: Polycystic kidney disease; autosomal dominan

Brain-predicted age difference mediates the association between PROMIS sleep impairment, and self-reported pain measure in persons with knee pain

Knee pain, the most common cause of musculoskeletal pain (MSK), constitutes a severe public health burden. Its neurobiological causes, however, remain poorly understood. Among many possible causes, it has been proposed that sleep problems could lead to an increase in chronic pain symptomatology, which may be driven by central nervous system changes. In fact, we previously found that brain cortical thickness mediated the relationship between sleep qualities and pain severity in older adults with MSK. We also demonstrated a significant difference in a machine-learning-derived brain-aging biomarker between participants with low-and high-impact knee pain. Considering this, we examined whether brain aging was associated with self-reported sleep and pain measures, and whether brain aging mediated the relationship between sleep problems and knee pain. Exploratory Spearman and Pearson partial correlations, controlling for age, sex, race and study site, showed a significant association of brain aging with sleep related impairment and self-reported pain measures. Moreover, mediation analysis showed that brain aging significantly mediated the effect of sleep related impairment on clinical pain and physical symptoms. Our findings extend our prior work demonstrating advanced brain aging among individuals with chronic pain and the mediating role of brain-aging on the association between sleep and pain severity. Future longitudinal studies are needed to further understand whether the brain can be a therapeutic target to reverse the possible effect of sleep problems on chronic pain

Predicting aging-related decline in physical performance with sparse electrophysiological source imaging

Objective: We introduce a methodology for selecting biomarkers from activation and connectivity derived from Electrophysiological Source Imaging (ESI). Specifically, we pursue the selection of stable biomarkers associated with cognitive decline based on source activation and connectivity patterns of resting-state EEG theta rhythm, used as predictors of physical performance decline in aging individuals measured by a Gait Speed (GS) slowing. Methods: Our two-step methodology involves estimating ESI using flexible sparse-smooth-nonnegative models, from which activation ESI (aESI) and connectivity ESI (cESI) features are derived. The Stable Sparse Classifier method then selects potential biomarkers related to GS changes. Results and Conclusions: Our predictive models using aESI outperform traditional methods such as the LORETA family. The models combining aESI and cESI features provide the best prediction of GS changes. Potential biomarkers from activation/connectivity patterns involve orbitofrontal and temporal cortical regions. Significance: The proposed methodology contributes to the understanding of activation and connectivity of GS-related ESI and provides features that are potential biomarkers of GS slowing. Given the known relationship between GS decline and cognitive impairment, this preliminary work opens novel paths to predict the progression of healthy and pathological aging and might allow an ESI-based evaluation of rehabilitation programs

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