Resting-state MRI reveals spontaneous physiological fluctuations in the kidney and tracks diabetic nephropathy in rats.

The kidneys maintain fluid-electrolyte balance and excrete waste in the presence of constant fluctuations in plasma volume and systemic blood pressure. The kidneys perform these functions to control capillary perfusion and glomerular filtration by modulating the mechanisms of autoregulation. An effect of these modulations are spontaneous, natural fluctuations in glomerular perfusion. Numerous other mechanisms can lead to fluctuations in perfusion and flow. The ability to monitor these spontaneous physiological fluctuations in vivo could facilitate the early detection of kidney disease. The goal of this work was to investigate the use of resting-state magnetic resonance imaging (rsMRI) to detect spontaneous physiological fluctuations in the kidney. We performed rsMRI of rat kidneys in vivo over 10 min, applying motion correction to resolve time series in each voxel. We observed spatially variable, spontaneous fluctuations in rsMRI signal between 0 and 0.3 Hz, in frequency bands associated with autoregulatory mechanisms. We further applied rsMRI to investigate changes in these fluctuations in a rat model of diabetic nephropathy. Spectral analysis was performed on time series of rsMRI signals in the kidney cortex and medulla. The power from spectra in specific frequency bands from the cortex correlated with severity of glomerular pathology caused by diabetic nephropathy. Finally, we investigated the feasibility of using rsMRI of the human kidney in two participants, observing the presence of similar, spatially variable fluctuations. This approach may enable a range of preclinical and clinical investigations of kidney function and facilitate the development of new therapies to improve outcomes in patients with kidney disease.NEW & NOTEWORTHY This work demonstrates the development and use of resting-state MRI to detect low-frequency, spontaneous physiological fluctuations in the kidney consistent with previously observed fluctuations in perfusion and potentially due to autoregulatory function. These fluctuations are detectable in rat and human kidneys, and the power of these fluctuations is affected by diabetic nephropathy in rats.

An unusual cause of neonatal hypothermia and shock in the emergency department: Diamond Blackfan Anemia.

Diamond Blackfan Anemia (DBA) is a rare disease characterized by anemia secondary to impaired red blood cell production from bone marrow failure. We present a case of infantile hypothermia and shock caused by this clinical pathology. A seven-week-old infant was brought to the emergency department by the father with the chief complaint of abnormal breathing and low activity level throughout the day. Medical history was unremarkable for both the patient and the family. On examination, the infant was breathing 30 breaths per minutes, had a heart rate of 116, and a core temperature of 33 degrees Celsius. The infant was ashen in color, limp, with grunted breathing and minimal movement. Numerous abnormal laboratory readings were reported, with the most significant being a hemoglobin of 1.7 and a hematocrit of 7.4. Emergent blood transfusion was initiated, and the patient was eventually air-lifted to a pediatric hospital two hours away. This case highlights the imperative of a thorough history and examination and consideration of a broad differential for neonatal hypothermia and shock, especially in the setting of no obvious bleeding.

DISPLACE study shows poor quality of transcranial doppler ultrasound for stroke risk screening in sickle cell anemia.

ABSTRACT: Children with sickle cell anemia (SCA) are at increased risk of stroke when compared with their age-based counterparts. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) previously demonstrated that with the use of transcranial Doppler ultrasound (TCD; Sickle Stroke Screen) and chronic red cell transfusion, the risk of stroke is reduced by over 90%. The STOP criteria detailed the type and method of measurement required; the time-averaged mean maximum velocity (TAMMV). Unfortunately, it has been difficult to adhere to the appropriate TAMMV measurements. The objectives of this study were to assess the quality of TCD and transcranial Doppler imaging (TCDi) reports to determine the report quality and accuracy. This is a subanalysis of the DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study. Over 12 000 TCD/TCDi reports were collected during this study from 28 institutions; 391 TCDs were reviewed for this subanalysis. There were significant variations in the vessels being assessed, the velocities used to define abnormal results, and who was interpreting the scans. In 52% of reports, it was impossible to identify whether the TAMMV was what was measured. Similarly, it was only clear in 42% of reports that the TAMMV was used to interpret the examination as normal/abnormal. Given this inconsistency, we strongly recommend standardization of TCD/TCDi reporting, specialized training for those performing and interpreting the scans in the use of TCD/TCDi in patients with SCA, internal quality assurance, and institutional quality improvement work to ensure appropriate use of this potentially lifesaving technology.

Intracranial aneurysms in sickle cell disease are associated with hemodynamic stress and anemia.

While hemodynamic stress plays a key role in aneurysm formation outside of SCD, its role is understudied in patients with SCD. We hypothesized that tissue-based markers of hemodynamic stress are associated with aneurysm presence in a prospective SCD cohort. Children and adults with SCD, with and without aneurysms, underwent longitudinal brain MRI/MRA to assess cerebral blood flow (CBF) and oxygen extraction fraction (OEF). Baseline characteristics were recorded. In the subgroup of adults, stepwise mixed-effect logistic regression examined clinical variables, CBF, and OEF as predictors of aneurysm presence. Cumulative rates of new aneurysm formation were estimated using Kaplan-Meier analyses. Forty-three aneurysms were found in 27 of 155 patients (17%). Most aneurysms were ≤ 3 mm and in the intracranial internal carotid artery. On univariate analysis, older age (p=0.07), lower hemoglobin (p=0.002), higher CBF (p=0.03), and higher OEF (p=0.02) were associated with aneurysm presence. On multivariable analysis, age and CBF remained independently associated with aneurysm presence. Seventy-six patients (49% of enrollment) received follow-up MRAs (median 3.5 years). No aneurysm grew or ruptured, however, seven new aneurysms developed in six patients. The three-year cumulative rate of aneurysm formation was 3.5%. In 155 patients with SCD, 17% had intracranial aneurysms. Three-year aneurysm formation rate was 3.5%, although limited by small longitudinal sample size and short follow-up duration. Aneurysm presence was associated with elevated CBF in adults, as a tissue-based marker of cerebral hemodynamic stress. Future studies may examine the predictive role of CBF in aneurysm development in SCD.