Detecting lumbar lesions in 99m Tc-MDP SPECT by deep learning: Comparison with physicians.

PURPOSE: 99m Tc-MDP single-photon emission computed tomography (SPECT) is an established tool for diagnosing lumbar stress, a common cause of low back pain (LBP) in pediatric patients. However, detection of small stress lesions is complicated by the low quality of SPECT, leading to significant interreader variability. The study objectives were to develop an approach based on a deep convolutional neural network (CNN) for detecting lumbar lesions in 99m Tc-MDP scans and to compare its performance to that of physicians in a localization receiver operating characteristic (LROC) study. METHODS: Sixty-five lesion-absent (LA) 99m Tc-MDP studies performed in pediatric patients for evaluating LBP were retrospectively identified. Projections for an artificial focal lesion were acquired separately by imaging a 99m Tc capillary tube at multiple distances from the collimator. An approach was developed to automatically insert lesions into LA scans to obtain realistic lesion-present (LP) 99m Tc-MDP images while ensuring knowledge of the ground truth. A deep CNN was trained using 2.5D views extracted in LP and LA 99m Tc-MDP image sets. During testing, the CNN was applied in a sliding-window fashion to compute a 3D "heatmap" reporting the probability of a lesion being present at each lumbar location. The algorithm was evaluated using cross-validation on a 99m Tc-MDP test dataset which was also studied by five physicians in a LROC study. LP images in the test set were obtained by incorporating lesions at sites selected by a physician based on clinical likelihood of injury in this population. RESULTS: The deep learning (DL) system slightly outperformed human observers, achieving an area under the LROC curve (AUCLROC ) of 0.830 (95% confidence interval [CI]: [0.758, 0.924]) compared with 0.785 (95% CI: [0.738, 0.830]) for physicians. The AUCLROC for the DL system was higher than that of two readers (difference in AUCLROC [ΔAUCLROC ] = 0.049 and 0.053) who participated to the study and slightly lower than that of two other readers (ΔAUCLROC  = -0.006 and -0.012). Another reader outperformed DL by a more substantial margin (ΔAUCLROC  = -0.053). CONCLUSION: The DL system provides comparable or superior performance than physicians in localizing small 99m Tc-MDP positive lumbar lesions.

Chronic Acalculous Cholecystitis in Children With Biliary Symptoms: Usefulness of Hepatocholescintigraphy.

OBJECTIVES: Chronic acalculous cholecystitis (CAC) increasingly is being diagnosed as a cause of recurring biliary symptoms in children, but its clinical diagnosis remains challenging. The primary objective was to evaluate the utility of hepatocholescintigraphy in pediatric patients with suspected CAC. A secondary objective was to describe their clinical follow-up after diagnosis. METHODS: Medical records of patients (aged 9-20 years) who underwent hepatocholescintigraphy from February 2008 to January 2012 were reviewed. Patients with gallstones, and with ≤1 year of clinical follow-up, and studies without gallbladder (GB) stimulation were excluded. GB ejection fraction (GBEF) of <35% after sincalide or fatty meal (Lipomul) stimulation were considered abnormal. Diagnosis of CAC was based on histopathology after cholecystectomy. Patients with negative GB pathology, or complete resolution of symptoms without surgery, or alternative diagnoses for persistent symptoms were considered to not have CAC. RESULTS: Eighty-three patients formed the study group (median age 14.9 years), of which 81.9% were girls. Median duration of symptoms and clinical follow-up were 6 months and 2.9 years, respectively. Fifty-two patients had at least 1 study with sincalide and 36 patients had at least 1 study with Lipomul. Initial cholescintigraphy was 95.0% sensitive and 73.0% specific in diagnosing CAC, with a negative predictive value of 97.9%. Of the 31 patients with abnormal GBEF, 22 underwent cholecystectomy with improvement in pain in 72.7%, whereas all of the 9 without surgery improved. CONCLUSIONS: Hepatocholescintigraphy is useful for excluding CAC, although the clinical implications of an abnormal GBEF need to be further defined.

Beyond current guidelines: reduction in minimum administered radiopharmaceutical activity with preserved diagnostic image quality in pediatric hepatobiliary scintigraphy.

PURPOSE: To determine if the minimum administered radiopharmaceutical activity for hepatobiliary scintigraphy can be reduced while preserving diagnostic image quality using enhanced planar processing (EPP). METHODS: A total of 40 infants between 10 and 270 days old (body mass 2.2 - 6.5 kg) had hepatobiliary scintigraphy during the period 2004 - 2010 following the intravenous administration of either (99m)Tc-mebrofenin (18 patients) or (99m)Tc-disofenin (22 patients). Due to the small size of these patients, they all received the minimum administered activity of 18.5 MBq consistent with the North American Consensus Guidelines. Six nuclear medicine physicians subjectively graded the acceptability of the image quality for clinical interpretation using a four-point scale (not acceptable, fair, good, excellent). Each physician independently graded seven image sets including the original study (full activity) and simulated reduced activity studies using binomial subsampling (50% of full activity, 25% of full activity and activity reduced by weight), with and without EPP. RESULTS: For full-activity studies, 98% were deemed acceptable by the six physicians for clinical interpretation. The percentages of acceptable 50% reduced activity studies with and without EPP were not significantly different from the percentage of acceptable full-activity studies (P = 0.193 and P = 0.998, respectively). The percentage of acceptable 25% reduced activity studies without EPP was significantly different from the percentage of acceptable full-activity studies (P < 0.001); however, this difference vanished when EPP was applied (P = 0.482). The activity reduced by weight ranged from 1.85 to 4.81 MBq (10% to 26% of full dose) and the percentages of acceptable studies with and without EPP were significantly different from the percentage of acceptable full-activity studies (P < 0.001 and P = 0.02, respectively). CONCLUSION: Clinically interpretable hepatobiliary scintigraphy images can be obtained in infants when the minimum administered activity is substantially reduced. Without EPP, clinically acceptable images may be produced with a reduction of 50%, and with EPP, a reduction of 75% or more may be possible.

Pediatric nuclear medicine and radiation dose.

Nuclear medicine is a unique and valuable method that contributes to the diagnosis and assessment of many diseases in children. Radiation exposures in children undergoing diagnostic nuclear medicine studies are low. Although in the past there has been a rather large variation of pediatric radiopharmaceutical administered activities, adhering to recent standards for pediatric radiopharmaceutical administered doses can help assure that the lowest administered activity are employed and that the diagnostic value of the studies is preserved. Radiation exposures in children can be reduced further by optimizing routine protocols, application of advanced image processing and potentially with the use of advanced imaging systems.

Sensory axon regeneration: rebuilding functional connections in the spinal cord.

Functional regeneration within the adult spinal cord remains a formidable task. A major barrier to regeneration of sensory axons into the spinal cord is the dorsal root entry zone. This region displays many of the inhibitory features characteristic of other central nervous system injuries. Several experimental treatments, including inactivation of inhibitory molecules (such as Nogo and chondroitin sulfate proteoglycans) or administration of neurotrophic factors (such as nerve growth factor, neurotrophin3, glial-derived neurotrophic factor and artemin), have been found to promote anatomical and functional regeneration across this barrier. However, there have been relatively few experiments to determine whether regenerating axons project back to their appropriate target areas within the spinal cord. This review focuses on recent advances in sensory axon regeneration, including studies assessing the ability of sensory axons to reconnect with their original synaptic targets.

Medication adherence and attitudes in patients with bipolar disorder and current versus past substance use disorder.

We examined the impact of substance use disorder (SUD) history among patients with bipolar I disorder (BD) in regards to medication-taking behaviors and attitudes. Interviews were conducted with inpatients hospitalized for BD, which included diagnostic instruments and measures of attitudes concerning psychiatric medications. We compared patients with BD and no history of SUD (BD-NH), BD and past history of SUD (BD-PH), and BD and current SUD (BD-C). The primary outcome variable was a standardized medication adherence ratio (SMAR) of [medication taken]/[medication prescribed]. Fifty-four patients with a BD diagnosis participated, which included BD-NH (n=26), BD-PH (n=19), and BD-C (n=9). The SMAR was significantly different among the three groups; post-hoc analyses revealed the SMAR was significantly lower among BD-C (M=0.70) compared to BD-NH (M=0.90) and BD-PH (M=0.97) patients. This finding remained significant after controlling for numerous patient characteristics. Attitudes regarding medications, measured by the Drug Attitude Inventory (DAI), were positive among a significantly higher percentage of BD-PH (89.47%) and BD-NH (65.38%) compared to BD-C (44.44%) patients. In conclusion, patients with BD-C demonstrated poor medication adherence and attitudes concerning medication management. Helping patients with BD achieve remission from SUD may lead to a more successful course of BD pharmacotherapy.

Gender-specific reduction in contraction is associated with increased estrogen receptor expression in single vascular smooth muscle cells of female rat.

Gender differences in the incidence of cardiovascular disease have been related to plasma estrogen levels; however, the role of vascular estrogen receptor (ER) subtypes in these sex differences is less clear. We tested whether the gender differences in vascular smooth muscle (VSM) function reflect differential expression/activity of ERalpha, ERbeta and the newly-identified GPR30. Single aortic VSM cells (VSMCs) were freshly isolated from male and female Sprague-Dawley rats, and their contraction to phenylephrine (PHE, 10(-5) M), AngII (10(-7) M) and membrane-depolarization by KCl (51 mM) was measured in the absence or presence of 10(-6) M 17beta-estradiol (E2, stimulant of most ERs), PPT (ERalpha agonist), DPN (ERbeta agonist), and ICI 182,780 (an ERalpha/ERbeta antagonist with GPR30 agonistic properties). The cells were fixed and fluorescently labeled with ERalpha, ERbeta or GPR30 antibody, and the subcellular distribution of ERs was examined using digital imaging microscopy. The mRNA expression and protein amount of aortic ER subtypes was examined using RT-PCR and Western blots. PHE, AngII, and KCl caused less contraction in VSMCs of females than males. Pretreatment of VSMCs with E2 reduced PHE-, AngII- and KCl-induced contraction in both males and females. PPT caused similar inhibition of PHE-, AngII- and KCl-induced contraction as E2, suggesting a role of ERalpha. DPN mainly inhibited PHE and KCl contraction, suggesting an interaction between ERbeta and Ca(2+) channels. ICI 182,780 did not reduce aortic VSMC contraction, suggesting little role for GPR30. RT-PCR and Western blots revealed greater expression of ERalpha and ERbeta in VSMCs of females than males, but similar amounts of GPR30. The total immunofluorescence signal for ERalpha and ERbeta was greater in VSMCs of females than males, and was largely localized in the nucleus. GPR30 fluorescence was similar in VSMCs of males and females, and was mainly in the cytosol. In PPT treated cells, nuclear ERalpha signal was enhanced. DPN did not affect the distribution of ERbeta, and ICI 182,780 did not significantly increase GPR30 in the cell surface. Thus, ER subtypes demonstrate similar responsiveness to specific agonists in VSMCs of male and female rats. The reduced contraction in VSMCs of females could be due to gender-related increase in the expression of ERalpha and ERbeta.

Nonmedical use of prescription stimulants and depressed mood among college students: frequency and routes of administration.

Studies demonstrate associations between nonmedical use of prescription stimulants (NMUPS) and depressed mood; however, relevance of NMUPS route of administration and frequency of use have not been examined. We hypothesized frequent NMUPS and nonoral routes would be significantly associated with depressed mood. A Web survey was self-administered by a probability sample of 3,639 undergraduate students at a large U.S. university. The survey contained substance use (e.g., frequency, route of administration) and depressed mood measurement. Past-year prevalence of NMUPS was 6.0% (n = 212). Approximately 50% of frequent or nonoral NMUPS reported depressed mood. Adjusted odds of depressed mood were over two times greater among frequent monthly NMUPS (adjusted odds ratio [AOR] = 2.3, 95% confidence interval [CI] = 1.01-5.15) and nonoral routes of administration (AOR = 2.2, 95% CI = 1.36-3.70), after controlling for other variables. Nonmedical users of prescription stimulants should be screened for depressed mood, especially those who report frequent and nonoral routes of administration.

Increased vascular angiotensin type 2 receptor expression and NOS-mediated mechanisms of vascular relaxation in pregnant rats.

Normal pregnancy is associated with reduced blood pressure (BP) and decreased pressor response to vasoconstrictors, even though the renin-angiotensin system is upregulated. Angiotensin II (ANG II) activates both angiotensin type 1 receptors (AT(1)Rs) and angiotensin type 2 receptors (AT(2)Rs). Although the role of the AT(1)R in vascular contraction is well documented, the role of the AT(2)R in vascular relaxation, particularly during pregnancy, is less clear. It was hypothesized that the decreased BP and vasoconstriction during pregnancy was, at least in part, due to changes in AT(2)R amount, distribution, and/or postreceptor mechanisms of vascular relaxation. To test this hypothesis, systolic BP was measured in virgin and pregnant (day 19) Sprague-Dawley rats. Isometric contraction/relaxation was measured in isolated aortic rings, and nitric oxide (NO) production was measured using 4-amino-5-methylamino-2',7'-difluorescein fluorescence. AT(1)R and AT(2)R mRNA expression and protein amount were measured in tissue homogenates using real-time RT-PCR and Western blots, and their local distribution was visualized in cryosections using immunohistochemistry and immunofluorescence. BP was lower in pregnant than virgin rats. Phenylephrine (Phe) caused concentration-dependent contraction that was reduced in the aorta of pregnant compared with virgin rats. Treatment with the AT(2)R antagonist PD-123319 caused greater enhancement of Phe contraction, and the AT(2)R agonist CGP-42112A caused greater relaxation of Phe contraction in the aorta of pregnant than virgin rats. ANG II plus the AT(1)R blocker losartan induced greater NO production in the aorta of pregnant than virgin rats. RT-PCR revealed increased mRNA expression of vascular endothelial NO synthase (eNOS), little change in AT(1)Rs, and increased AT(2)Rs in pregnant compared with virgin rats. Western blots revealed an increased protein amount of activated phospho-eNOS, little change in AT(1)Rs, and increased AT(2)Rs in pregnant compared with virgin rats. Immunohistochemistry and immunofluorescence analysis in aortic sections of virgin rats revealed abundant AT(1)R staining in tunica media that largely colocalized with actin in vascular smooth muscle and less AT(2)Rs mainly in the tunica intima and endothelium. In pregnant rats, AT(1)R staining in the smooth muscle layer and adventitia was reduced, and endothelial AT(2)R staining was enhanced. These data suggest an enhanced AT(2)R-mediated vascular relaxation pathway involving increased expression/activity of endothelial AT(2)Rs and increased postreceptor activated phospho-eNOS, which may contribute to the decreased BP during pregnancy.