MRI-Guided High-Dose-Rate Gynecologic Brachytherapy Using an MR-Linac as an MR Simulator: A Single Institutional Experience.

PURPOSE: The goal of this study was to commission the use of a magnetic resonance linear accelerator (MR-linac; Unity) for imaging of gynecologic high-dose-rate (HDR) brachytherapy. This included optimizing imaging protocols and workflow development. METHODS AND MATERIALS: T1-weighted and T2-weighted HDR imaging protocols were optimized on the Unity for HDR gynecologic imaging and treatment planning. Phantom measurements using these protocols were performed to determine geometric distortion and to assess reconstruction accuracy of the applicator compared with the ground truth computed tomography image. A treatment plan was created within the treatment planning system that was then delivered to a phantom. New workflows were developed which were tested with a full dry run with a healthy volunteer including patient transfer, anesthesia considerations, and data transfer. Validation of the workflow was completed on 1 patient who received imaging on both the Unity magnetic resonance imaging (MRI) and on a dedicated 3 Tesla MRI simulator. RESULTS: Imaging analysis results were favorable with MR-linac images with a maximum distortion of 0.96 mm and a 1.36-mm over a 350-mm diameter spherical volume on the T1- and T2-weighted images, respectively, and the maximum effect of the applicator was 0.36 ppm of the main magnetic field. Reconstruction uncertainties of the Venezia applicator's tandem and 2 lunar-ovoids on the MR-linac images were within the 2-mm tolerance of the International Commission on Radiation Units and Measurements Report 89. Treatment planning and delivery was performed on the MR-HDR quality assurance phantom without issue. Dry run and healthy volunteer imaging showed adequate performance of both vital monitoring and HDR equipment. For the patient for which both the Unity MRI and 3 Tesla images were acquired, 95.78% and 95.80% of the high risk clinical target volume received 100% of the dose, respectively. Both plans were considered clinically acceptable. CONCLUSIONS: Unity MR-linac images were successfully used in gynecologic HDR brachytherapy treatment planning, and a usable workflow was established.

Development and implementation of optimized endogenous contrast sequences for delineation in adaptive radiotherapy on a 1.5T MR-linear-accelerator: a prospective R-IDEAL stage 0-2a quantitative/qualitative evaluation of in vivo site-specific quality-assurance using a 3D T2 fat-suppressed platform for head and neck cancer.

Purpose: To improve segmentation accuracy in head and neck cancer (HNC) radiotherapy treatment planning for the 1.5T hybrid magnetic resonance imaging/linear accelerator (MR-Linac), three-dimensional (3D), T2-weighted, fat-suppressed magnetic resonance imaging sequences were developed and optimized. Approach: After initial testing, spectral attenuated inversion recovery (SPAIR) was chosen as the fat suppression technique. Five candidate SPAIR sequences and a nonsuppressed, T2-weighted sequence were acquired for five HNC patients using a 1.5T MR-Linac. MR physicists identified persistent artifacts in two of the SPAIR sequences, so the remaining three SPAIR sequences were further analyzed. The gross primary tumor volume, metastatic lymph nodes, parotid glands, and pterygoid muscles were delineated using five segmentors. A robust image quality analysis platform was developed to objectively score the SPAIR sequences on the basis of qualitative and quantitative metrics. Results: Sequences were analyzed for the signal-to-noise ratio and the contrast-to-noise ratio and compared with fat and muscle, conspicuity, pairwise distance metrics, and segmentor assessments. In this analysis, the nonsuppressed sequence was inferior to each of the SPAIR sequences for the primary tumor, lymph nodes, and parotid glands, but it was superior for the pterygoid muscles. The SPAIR sequence that received the highest combined score among the analysis categories was recommended to Unity MR-Linac users for HNC radiotherapy treatment planning. Conclusions: Our study led to two developments: an optimized, 3D, T2-weighted, fat-suppressed sequence that can be disseminated to Unity MR-Linac users and a robust image quality analysis pathway that can be used to objectively score SPAIR sequences and can be customized and generalized to any image quality optimization protocol. Improved segmentation accuracy with the proposed SPAIR sequence will potentially lead to improved treatment outcomes and reduced toxicity for patients by maximizing the target coverage and minimizing the radiation exposure of organs at risk.

Modulation of neural activation following treatment of hepatic encephalopathy.

OBJECTIVE: To measure changes in psychometric state, neural activation, brain volume (BV), and cerebral metabolite concentrations during treatment of minimal hepatic encephalopathy. METHODS: As proof of principle, 22 patients with well-compensated, biopsy-proven cirrhosis of differing etiology and previous minimal hepatic encephalopathy were treated with oral l-ornithine l-aspartate for 4 weeks. Baseline and 4-week clinical review, blood chemistry, and psychometric evaluation (Psychometric Hepatic Encephalopathy Score and Cognitive Drug Research Score) were performed. Whole-brain volumetric and functional MRI was conducted using a highly simplistic visuomotor task, together with proton magnetic resonance spectroscopy of the basal ganglia. Treatment-related changes in regional BV and neural activation change (blood oxygenation level dependent) were assessed. RESULTS: Although there was no change in clinical, biochemical state, basal ganglia magnetic resonance spectroscopy, or in regional BV, there were significant improvements in Cognitive Drug Research Score (+1.2, p = 0.003) and Psychometric Hepatic Encephalopathy Score (+1.5, p = 0.003) with treatment. This cognitive amelioration was accompanied by changes in blood oxygenation level-dependent activation in the posterior cingulate and ventral medial prefrontal cortex, 2 regions that form part of the brain's structural and metabolic core. In addition, there was evidence of greater visual cortex activation. CONCLUSIONS: These structurally interconnected regions all showed increased function after successful encephalopathy treatment. Because no regional change in BV was observed, this implies that mechanisms unrelated to astrocyte volume regulation were involved in the significant improvement in cognitive performance.

Anaesthesia for caesarean section in women with complex cardiac disease: 34 cases using the Braun Spinocath spinal catheter.

BACKGROUND: Cardiac disease in pregnancy is now the leading medical cause of maternal mortality in the UK. Whilst anaesthesia has not been the precipitant of this morbidity, its safety cannot be taken for granted. Spinal catheter anaesthesia, a relatively uncommon choice in obstetric practice, offers the potential of maintaining haemodynamic stability through accurate and gradual titration of neuraxial blockade. METHODS: Thirty-four women with cardiac disease requiring caesarean section were selected for spinal catheter anaesthesia. All received invasive arterial pressure measurement but in only two were central venous catheters sited. After inserting a 24-gauge Braun Spinocath, spinal anaesthesia was induced using diamorphine 300 microg and 0.5% hyperbaric bupivacaine in 0.25-mL increments. Technical problems, block quality and haemodynamic stability were recorded. RESULTS: Successful anaesthesia was achieved in 33 women. Spinal catheterisation proved impossible in one case, but the catheter was successfully used to provide epidural anaesthesia. There were no conversions to general anaesthesia. Eight women (24%) received supplementation with intravenous alfentanil, but all reported high satisfaction. Mild, transient hypotension occurred in six women (18%), and there was one case of vasovagal syncope induced by rapid exteriorisation of the uterus. Three patients (8.8%) experienced post dural puncture headache requiring a blood patch; two had received repeat dural puncture during catheter insertion. CONCLUSIONS: Incremental spinal catheter anaesthesia offers effective anaesthesia with excellent haemodynamic control. Post dural puncture headache is of concern, and whilst it may be addressed by product modification, it currently limits widespread use of the Braun Spinocath in obstetric practice.

Human 5-HT transporter availability predicts amygdala reactivity in vivo.

The amygdala plays a central role in fear conditioning, emotional processing, and memory modulation. A postulated key component of the neurochemical regulation of amygdala function is the neurotransmitter 5-hydroxytryptamine (5-HT), and synaptic levels of 5-HT in the amygdala and elsewhere are critically regulated by the 5-HT transporter (5-HTT). The aim of this study was to directly examine the relationship between 5-HTT availability and amygdala activity using multimodal [positron emission tomography (PET) and functional magnetic resonance imaging (fMRI)] imaging measures in the same individuals. Healthy male volunteers who had previously undergone an [11C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]-DASB) PET scan to determine 5-HTT availability completed an fMRI emotion recognition task. [11C]-DASB binding potential values were calculated for the amygdala using arterial input function and linear graphical (Logan) analysis. fMRI was performed on a 3T Philips Intera scanner, and data were analyzed using SPM2 (Wellcome Department Imaging Neuroscience, University College London). Percentage signal change during the task was extracted from the amygdala using MarsBaR (Brett et al., 2002). fMRI analysis revealed significant amygdala activation during the emotion recognition task. Region of interest analyses demonstrated a significant negative correlation between fMRI signal change in the left amygdala and 5-HTT availability in the left amygdala, with 5-HTT availability accounting for approximately 42% of the variability in left amygdala activity. Our novel in vivo data highlight the central importance of the serotonergic system in the responsiveness of the human amygdala during emotional processing.

Functional integration across brain regions improves speech perception under adverse listening conditions.

Speech perception is supported by both acoustic signal decomposition and semantic context. This study, using event-related functional magnetic resonance imaging, investigated the neural basis of this interaction with two speech manipulations, one acoustic (spectral degradation) and the other cognitive (semantic predictability). High compared with low predictability resulted in the greatest improvement in comprehension at an intermediate level of degradation, and this was associated with increased activity in the left angular gyrus, the medial and left lateral prefrontal cortices, and the posterior cingulate gyrus. Functional connectivity between these regions was also increased, particularly with respect to the left angular gyrus. In contrast, activity in both superior temporal sulci and the left inferior frontal gyrus correlated with the amount of spectral detail in the speech signal, regardless of predictability. These results demonstrate that increasing functional connectivity between high-order cortical areas, remote from the auditory cortex, facilitates speech comprehension when the clarity of speech is reduced.

Positive emotions preferentially engage an auditory-motor "mirror" system.

Social interaction relies on the ability to react to communication signals. Although cortical sensory-motor "mirror" networks are thought to play a key role in visual aspects of primate communication, evidence for a similar generic role for auditory-motor interaction in primate nonverbal communication is lacking. We demonstrate that a network of human premotor cortical regions activated during facial movement is also involved in auditory processing of affective nonverbal vocalizations. Within this auditory-motor mirror network, distinct functional subsystems respond preferentially to emotional valence and arousal properties of heard vocalizations. Positive emotional valence enhanced activation in a left posterior inferior frontal region involved in representation of prototypic actions, whereas increasing arousal enhanced activation in presupplementary motor area cortex involved in higher-order motor control. Our findings demonstrate that listening to nonverbal vocalizations can automatically engage preparation of responsive orofacial gestures, an effect that is greatest for positive-valence and high-arousal emotions. The automatic engagement of responsive orofacial gestures by emotional vocalizations suggests that auditory-motor interactions provide a fundamental mechanism for mirroring the emotional states of others during primate social behavior. Motor facilitation by positive vocal emotions suggests a basic neural mechanism for establishing cohesive bonds within primate social groups.

Audit of the influence of body mass index on the performance of epidural analgesia in labour and the subsequent mode of delivery.

OBJECTIVE: To assess the influence of body mass index (BMI) on the performance of epidural analgesia in labour and the subsequent mode of delivery. DESIGN: A retrospective audit of prospectively collected quality assurance data. SETTING: The delivery suite of Leeds General Infirmary, Leeds, UK. This is a 4500-delivery teaching hospital unit. POPULATION: All women receiving epidural analgesia during labour in our unit between April 1997 and December 2005. METHODS: Epidural recipients were divided into BMI groups according to World Health Organization (WHO) categories and compared for indices of epidural performance and mode of delivery. MAIN OUTCOME MEASURES: Midwife and patient satisfaction scores with epidural analgesia, epidural resite rates, and mode of delivery. RESULTS: Data from 13 299 epidural recipients were analysed. Using WHO definitions, 22.8% were of normal body mass, 41.9% were overweight, 31.9% obese, and 3.4% morbidly obese. Epidurals were more likely to fail as BMI increased, as judged by midwife satisfaction scores (P < 0.001) and epidural resite rates (P < 0.01). This trend was not seen for maternal satisfaction scores using the WHO BMI categories. However, if women with BMI below 30 kg/m2 were grouped together, a significant trend was found (P < 0.01). BMI had no influence on vaginal instrumental deliveries, but caesarean section rates rose from 11.5% in women of normal BMI to 29.2% in the morbidly obese women (P < 0.001). CONCLUSIONS: Obesity increases the incidence of analgesic failure and the need for resite of epidurals. The caesarean section rate among epidural recipients increases dramatically as BMI rises.

MR elastography of the liver: preliminary results.

PURPOSE: To develop a method for measuring liver stiffness with magnetic resonance (MR) elastography and to prospectively test this technique in healthy volunteers and patients with liver fibrosis. MATERIALS AND METHODS: This HIPAA-compliant study was approved by an institutional review board, and informed consent was obtained from each subject. First, to determine the feasibility of applying shear waves to the liver, a pneumatic acoustic wave generator was developed and tested by using a tissue-simulating gel phantom with ribs on one side and without ribs on the other. The effect of interposed ribs on stiffness measurements was tested. Then, liver stiffness was measured with MR elastography in 12 healthy volunteers (eight men, four women; mean age, 26.7 years; age range, 19-39 years) by using the subcostal approach and the transcostal approach and in 12 patients with chronic liver disease (six men, six women; mean age, 50.5 years; age range, 36-60 years) by using the transcostal approach. Various statistical analyses were performed to assess all measurements. RESULTS: Ex vivo, interposed ribs reduced shear wave amplitude but did not hinder stiffness measurements. In volunteers, the transcostal approach surprisingly yielded better shear waves in the liver than did the subcostal approach. The mean liver shear stiffness was significantly lower in volunteers (mean, 2.0 kPa +/- 0.3 [standard deviation]) than it was in patients with liver fibrosis (mean, 5.6 kPa +/- 5.0; median, 3.7 kPa; range, 2.7-19.2 kPa; P < .001). CONCLUSION: MR elastography of the liver is feasible and shows promise as a quantitative method for noninvasive assessment of liver fibrosis.

Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encephalopathy.

Hepatic encephalopathy (HE) is a common neuro-psychiatric abnormality, which complicates the course of patients with liver disease and results from hepatocellular failure and/or portosystemic shunting. The manifestations of HE are widely variable and involve a spectrum from mild subclinical disturbance to deep coma. Research interest has focused on the role of circulating gut-derived toxins, particularly ammonia, the development of brain swelling and changes in cerebral neurotransmitter systems that lead to global CNS depression and disordered function. Until recently the direct investigation of cerebral function has been difficult in man. However, new magnetic resonance imaging (MRI) techniques provide a non-invasive means of assessment of changes in brain volume (coregistered MRI) and impaired brain function (fMRI), while proton magnetic resonance spectroscopy (1H MRS) detects changes in brain biochemistry, including direct measurement of cerebral osmolytes, such as myoinositol, glutamate and glutamine which govern processes intrinsic to cellular homeostasis, including the accumulation of intracellular water. The concentrations of these intracellular osmolytes alter with hyperammonaemia. MRS-detected metabolite abnormalities correlate with the severity of neuropsychiatric impairment and since MR spectra return towards normal after treatment, the technique may be of use in objective patient monitoring and in assessing the effectiveness of various treatment regimens.

Aortocaval compression in pregnancy: the effect of changing the degree and direction of lateral tilt on maternal cardiac output.

IMPLICATIONS: Using thoracic bioimpedance to measure maternal cardiac output, we were unable to demonstrate any benefit from increasing the magnitude of lateral table tilt. This implies that it is unnecessary to use extremes of lateral table tilt in healthy pregnancy although this may not apply to women with cardiac compromise or regional anesthesia.

Measurement of muscle activity with magnetic resonance elastography.

OBJECTIVE: To non-invasively determine muscle activity. DESIGN: A correlation analysis study. BACKGROUND: Electromyography is traditionally used to measure the electrical activity of a muscle and can be used to estimate muscle contraction intensity. This approach, however, is limited not only in terms of the volume of tissue that can be monitored, but must be invasive if deep lying muscles are studied. We wished to avoid these limitations and used magnetic resonance elastography in an attempt to non-invasively determine muscle activity. This novel approach uses a conventional MRI system. However, in addition to the imaging gradients, an oscillating, motion sensitizing field gradient is applied to detect mechanical waves that have been generated within the tissue. The wavelength correlates with the stiffness of the muscle and hence with the activity of the muscle. METHODS: Six volunteers (mean age: 30.1 years, range: 27-36 years) without orthopedic or neuromuscular abnormalities, lay supine with their legs within the coil of a MRI scanner. The wavelengths of mechanically generated shear waves in the tibialis anterior, medial and lateral head of the gastrocnemius and the soleus were measured as the subjects resisted ankle plantar-flexing (8.2 and 16.4 nm) and dorsi-flexing (20.2 and 40.4 nm) moments. The findings were then compared to EMG data collected under the same loading conditions. RESULTS: Magnetic resonance elastography wavelengths were linearly correlated to the muscular activity as defined by electromyography. (TA, R(2)=0.89, P=0.02; MG, R(2)=0.82, P=0.05; LG, R(2)=0.88, P=0.03; S, R(2)=0.90, P=0.02) CONCLUSIONS: Magnetic resonance elastography may be a promising tool for the non-invasive determination of muscle activity. RELEVANCE: Magnetic resonance elastography has potential as the basis for a new non-invasive approach to study in vivo muscle function.

Meningococcal meningitis after combined spinal-epidural analgesia.

We present a case of bacterial meningitis in a 32-year-old parturient following combined spinal-epidural analgesia for labour. The patient made a full recovery with no residual neurological sequelae, but important lessons were learnt. Firstly, investigating obstetricians and physicians were unaware that a combined spinal-epidural technique included an intrathecal component, so did not consider treating organisms that might be acquired by this route. Anaesthetists, on the other hand, in the absence of an isolated organism, saw this as a likely combined spinal-epidural complication. Infectious disease experts eventually diagnosed community-acquired meningococcal meningitis by analysing bacterial deoxyribonucleic acid (DNA) fragments using polymerase chain reaction studies. This test and the management of suspected meningitis in the post-partum period are discussed.

Haemodynamic changes caused by oxytocin during caesarean section under spinal anaesthesia.

The haemodynamic effects of oxytocin receive scant attention in pharmacology texts, but may be clinically significant in vulnerable patients. Despite prescriber information recommending a dose of 5 international units by slow i.v. injection, it is the authors' experience that it is very common practice in the UK to give 10 units as a rapid injection. We therefore conducted a randomised, double-blind study of the haemodynamic changes induced by rapid bolus of 5 or 10 units of oxytocin in 34 healthy term parturients at caesarean section under spinal anaesthesia. There was a small but statistically significant (P < 0.05) reduction in mean arterial pressure from baseline 30 s after a 10-unit bolus. However, large, statistically significant increases in heart rate and cardiac output occurred 1 min after 5 units and 2 min after 10 units. These changes peaked 1 min after oxytocin administration and were greater in the 10-unit group (P < 0.05). The importance of these findings is that some women with hypovolaemia or cardiac disease may be unable to mount these compensatory responses and are therefore at risk of haemodynamic collapse after oxytocin boluses. This has been illustrated by a maternal death reported to the Confidential Enquiries into Maternal Deaths in the United Kingdom. The need to adhere to a dose regimen of 5 units by slow injection needs re-emphasis, but no evidence exists to claim that even this will be haemodynamically inert. We therefore recommend that oxytocin boluses be avoided in women with hypovolaemia or cardiac disease.

Magnetic resonance elastography: non-invasive mapping of tissue elasticity.

Magnetic resonance elastography (MRE) is a phase-contrast-based MRI imaging technique that can directly visualize and quantitatively measure propagating acoustic strain waves in tissue-like materials subjected to harmonic mechanical excitation. The data acquired allows the calculation of local quantitative values of shear modulus and the generation of images that depict tissue elasticity or stiffness. This is significant because palpation, a physical examination that assesses the stiffness of tissue, can be an effective method of detecting tumors, but is restricted to parts of the body that are accessible to the physician's hand. MRE shows promise as a potential technique for 'palpation by imaging', with possible applications in tumor detection (particularly in breast, liver, kidney and prostate), characterization of disease, and assessment of rehabilitation (particularly in muscle). We describe MRE in the context of other recent techniques for imaging elasticity, discuss the processing algorithms for elasticity reconstruction and the issues and assumptions they involve, and present recent ex vivo and in vivo results.

Incremental spinal anaesthesia for elective Caesarean section in a patient with Eisenmenger's syndrome.

We describe a new approach to anaesthesia for elective Caesarean section in a woman with Eisenmenger's syndrome. Incremental regional anaesthesia was performed using a microspinal catheter and haemodynamic monitoring included transthoracic bioimpedance cardiography. This approach allowed the disadvantages of general anaesthesia and invasive cardiac output monitoring to be avoided.