PET Imaging of Leg Arteries for Determining the Input Function in PET/MRI Brain Studies Using a Compact, MRI-compatible PET System.

In this study, we used a compact, high-resolution, and MRI-compatible PET camera (VersaPET) to assess the feasibility of measuring the image-derived input function (IDIF) from arteries in the leg with the ultimate goal of enabling fully quantitative PET brain imaging without blood sampling. We used this approach in five 18F-FDG PET/MRI brain studies in which the input function was also acquired using the gold standard of serial arterial blood sampling. After accounting for partial volume, dispersion, and calibration effects, we compared the metabolic rates of glucose (MRglu) quantified from VersaPET IDIFs in 80 brain regions to those using the gold standard and achieved a bias and variability of <5% which is within the range of reported test-retest values for this type of study. We also achieved a strong linear relationship (R2 >0.97) against the gold standard across regions. The results of this preliminary study are promising and support further studies to optimize methods, validate in a larger cohort, and extend to the modeling of other radiotracers.

Development and evaluation of a multimodal marker of major depressive disorder.

This study aimed to identify biomarkers of major depressive disorder (MDD), by relating neuroimage-derived measures to binary (MDD/control), ordinal (severe MDD/mild MDD/control), or continuous (depression severity) outcomes. To address MDD heterogeneity, factors (severity of psychic depression, motivation, anxiety, psychosis, and sleep disturbance) were also used as outcomes. A multisite, multimodal imaging (diffusion MRI [dMRI] and structural MRI [sMRI]) cohort (52 controls and 147 MDD patients) and several modeling techniques-penalized logistic regression, random forest, and support vector machine (SVM)-were used. An additional cohort (25 controls and 83 MDD patients) was used for validation. The optimally performing classifier (SVM) had a 26.0% misclassification rate (binary), 52.2 ± 1.69% accuracy (ordinal) and r = .36 correlation coefficient (p < .001, continuous). Using SVM, R2 values for prediction of any MDD factors were <10%. Binary classification in the external data set resulted in 87.95% sensitivity and 32.00% specificity. Though observed classification rates are too low for clinical utility, four image-based features contributed to accuracy across all models and analyses-two dMRI-based measures (average fractional anisotropy in the right cuneus and left insula) and two sMRI-based measures (asymmetry in the volume of the pars triangularis and the cerebellum) and may serve as a priori regions for future analyses. The poor accuracy of classification and predictive results found here reflects current equivocal findings and sheds light on challenges of using these modalities for MDD biomarker identification. Further, this study suggests a paradigm (e.g., multiple classifier evaluation with external validation) for future studies to avoid nongeneralizable results.

[11C]Harmine Binding to Brain Monoamine Oxidase A: Test-Retest Properties and Noninvasive Quantification.

PURPOSE: Inhibition of the isoform A of monoamine oxidase (MAO-A), a mitochondrial enzyme catalyzing deamination of monoamine neurotransmitters, is useful in treatment of depression and anxiety disorders. [11C]harmine, a MAO-A PET radioligand, has been used to study mood disorders and antidepressant treatment. However, [11C]harmine binding test-retest characteristics have to date only been partially investigated. Furthermore, since MAO-A is ubiquitously expressed, no reference region is available, thus requiring arterial blood sampling during PET scanning. Here, we investigate [11C]harmine binding measurements test-retest properties; assess effects of using a minimally invasive input function estimation on binding quantification and repeatability; and explore binding potentials estimation using a reference region-free approach. PROCEDURES: Quantification of [11C]harmine distribution volume (VT) via kinetic models and graphical analyses was compared based on absolute test-retest percent difference (TRPD), intraclass correlation coefficient (ICC), and identifiability. The optimal procedure was also used with a simultaneously estimated input function in place of the measured curve. Lastly, an approach for binding potentials quantification in absence of a reference region was evaluated. RESULTS: [11C]harmine VT estimates quantified using arterial blood and kinetic modeling showed average absolute TRPD values of 7.7 to 15.6 %, and ICC values between 0.56 and 0.86, across brain regions. Using simultaneous estimation (SIME) of input function resulted in VT estimates close to those obtained using arterial input function (r = 0.951, slope = 1.073, intercept = - 1.037), with numerically but not statistically higher test-retest difference (range 16.6 to 22.0 %), but with overall poor ICC values, between 0.30 and 0.57. CONCLUSIONS: Prospective studies using [11C]harmine are possible given its test-retest repeatability when binding is quantified using arterial blood. Results with SIME of input function show potential for simplifying data acquisition by replacing arterial catheterization with one arterial blood sample at 20 min post-injection. Estimation of [11C]harmine binding potentials remains a challenge that warrants further investigation.

Efficacy of Caudal Clonidine and Fentanyl on Analgesia, Neuroendocrine Stress Response and Emergence Agitation in Children Undergoing Lower Abdominal Surgeries Under General Anaesthesia with Sevoflurane.

INTRODUCTION: Clonidine has proved to be effective drug for postoperative analgesia but it's efficacy to alter neuroendocrine stress response and emergence agitation is unknown. This study was conducted to assess and compare the efficacy of caudal fentanyl vs. clonidine for analgesia, blunting of neuroendocrine stress responses (NESR) and emergence agitation (EA) following sevoflurane anaesthesia. MATERIALS AND METHODS: This prospective, randomized, double blind study enrolled 60 children undergoing infraumbilical surgery. Three groups of 20 each were assigned to receive caudal block with either bupivacaine 0.25% 1 ml/kg with normal saline (group I) or bupivacaine 0.25% 1 ml/kg and 1 microgram*kg-1fentanyl (group II), or bupivacaine 0.25% 1 ml/kg and 3 µg/kg clonidine [group III]. Postoperative analgesia, sedation, NESR, emergence agitation and side effects were observed. RESULTS: VAS score at two hours was significantly less in group III (0.60± 0.60) than in group I (1.80± 0.41) and group II (1.25± 0.44), the time to rescue analgesia was also significantly greater in group III (8.03+0.41hours) than groups I and II (4.15± 0.54 hours) and (6.18± 0.5hours) respectively. The EA scores were significantly better in Group III but patients were significantly more sedated postoperatively. Intraoperatively, NESR was blunted in all the groups and the markers of NESR were lowest in group III. CONCLUSION: Caudal clonidine in a dose of 3 µg/kg prolongs analgesia and decreases emergence agitation as compared to bupivacaine alone or with fentanyl 1µg/kg. Modulation of the neuroendocrine stress response was observed in all the investigated groups though the indicators were lowest in clonidine group.

Efficacy of caudal fentanyl and ketamine on post-operative pain and neuroendocrine stress response in children undergoing infraumbilical and perineal surgery: A pilot study.

BACKGROUND AND AIMS: It is well-known that neuroendocrine stress response (NESR) occurs in children and it can be modified by caudal block. However, there is paucity of literature comparing caudal fentanyl and ketamine on NESR. The present study was aimed to compare the analgesic efficacy of these caudal adjuvants and their effect on (NESR) in children undergoing infraumbilical and perineal surgery. MATERIALS AND METHODS: A total of 60 children undergoing infraumbilical surgery were included in this randomized, double-blind study. Three groups of 20 each were assigned to receive caudal block with bupivacaine 0.25% 1 ml/kg along with either 0.9% normal saline (Group I) 1 µg/kg fentanyl (Group II) or 0.5 mg/kg ketamine (Group III). Modified visual analogue scale (VAS) was used for assessment of post-operative pain, and stress response was assessed by blood glucose, serum cortisol and insulin levels at various time intervals. RESULTS: VAS scores were significantly lower in the ketamine group at all-time intervals upto 4 h (P < 0.05). Patients in ketamine group required rescue analgesia significantly later (8.23 h) when compared to fentanyl (5.95 h) and bupivacaine group (4.10 h). Caudal block led to significant decrease in cortisol and insulin levels within the groups however this significance was not achieved between groups. CONCLUSION: Caudal ketamine in a dose of 0.5 mg/kg provides prolonged analgesia when compared to fentanyl 1 µg/kg. Blunting of the NESR was observed in all the groups though the indicators of the response were lowest with ketamine.

Acute barium intoxication following ingestion of soap water solution.

We present a rare case in which a young girl ingested a solution of a hair-removing soap. The ingestion resulted in profound hypokalemia and severe acidosis leading to flaccid paralysis, respiratory arrest and ventricular arrhythmias. Ultimately the patient made complete recovery. The soapwas found to contain barium sulfide. The degree of paralysis and acidosis appeared to be directly related to serum potassium levels.

Analgesic efficacy of two doses of intrathecal midazolam with bupivacaine in patients undergoing cesarean delivery.

OBJECTIVES: In this prospective, randomized, double-blind, placebo-controlled study, we investigated the postoperative analgesic efficacy of 2 doses of intrathecal midazolam as an adjunct to bupivacaine for spinal anesthesia. METHODS: Sixty patients undergoing elective cesarean delivery under spinal anesthesia were allocated randomly to 3 groups: group B, 2 mL hyperbaric bupivicaine 0.5%; group BM1, 2 mL bupivacaine plus midazolam 1 mg (preservative free); and group BM2, 2 mL bupivicaine plus midazolam 2 mg. RESULTS: The mean duration of postoperative analgesia (determined by request for rescue medication) was 3.8 +/- 0.5 hours in group B compared with 4.3 +/- 0.7 hours in group BM1 (P = .18), and 6.1 +/- 1.0 hours in group BM2 (P = .001). Supplemental analgesic requirements with diclofenac were significantly less in group BM2 (93 +/- 29 mg) compared with group B (145 +/- 12 mg) and group BM1 (148 +/- 16 mg, P < .001). Time to block regression was longer in group B (182 +/- 30 minutes) compared with group BM1 (152 +/- 32 minutes) and group B (126 +/- 20 minutes) (both P < .001). Arterial pressure, heart rate, oxygen saturation, sedation score, and time to first void were comparable between groups. Group B had a significantly higher incidence of nausea and vomiting than groups BM1 and BM2 (P = .02). No neurologic deficits were observed. CONCLUSIONS: Intrathecal midazolam 2 mg provided a moderate prolongation of postoperative analgesia when used as an adjunct to bupivacaine in patients undergoing cesarean delivery. Intrathecal midazolam, 1 mg and 2 mg, decreased postoperative nausea and vomiting.

Psychopharmacologic management during cancer treatment.

The patient with cancer faces many stressors during the course of the illness, including fears of death, disability, disfigurement, dependency, and abandonment, as well as disruptions in relationships, role functioning, and financial status. Although such concerns are universal, the level of psychological distress varies depending on psychologic, medical, and social factors. As people are becoming more optimistic about cancer survival as a result of improved cancer treatments, patients and their families are more interested in quality-of-life issues, including psychologic well-being and treatment of psychiatric issues, during and after cancer treatment. In this article, we discuss the psychopharmacologic management of the commonly seen psychiatric syndromes of anxiety, depression and delirium during cancer treatment.