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Purpose: To evaluate the influence of the confounding factors, direct water saturation (DWS), and magnetization transfer contrast (MTC) effects on measured Z-spectra and amide proton transfer (APT) contrast in brain tumors., Methods: High-grade glioma patients were scanned using an RF saturation-encoded 3D MR fingerprinting (MRF) sequence at 3 T. For MRF reconstruction, a recurrent neural network was designed to learn free water and semisolid macromolecule parameter mappings of the underlying multiple tissue properties from saturation-transfer MRF signals. The DWS spectra and MTC spectra were synthesized by solving Bloch-McConnell equations and evaluated in brain tumors., Results: The dominant contribution to the saturation effect at 3.5 ppm was from DWS and MTC effects, but 25%-33% of the saturated signal in the gadolinium-enhancing tumor (13%-20% for normal tissue) was due to the APT effect. The APT # signal of the gadolinium-enhancing tumor was significantly higher than that of the normal-appearing white matter (10.1% vs. 8.3% at 1 μT and 11.2% vs. 7.8% at 1.5 μT)., Conclusion: The RF saturation-encoded MRF allowed us to separate contributions to the saturation signal at 3.5 ppm in the Z-spectrum. Although free water and semisolid MTC are the main contributors, significant APT contrast between tumor and normal tissues was observed., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To implement rosette readout trajectories with compressed sensing reconstruction for fast and motion-robust CEST and magnetization transfer contrast imaging with inherent correction of B 0 inhomogeneity., Methods: A pulse sequence was developed for fast saturation transfer imaging using a stack of rosette trajectories with a higher sampling density near the k-space center. Each rosette lobe was segmented into two halves to generate dual-echo images. B 0 inhomogeneities were estimated using the phase difference between the images and corrected subsequently. The rosette-based imaging was evaluated in comparison to a fully sampled Cartesian trajectory and demonstrated on CEST phantoms (creatine solutions and egg white) and healthy volunteers at 3 T., Results: Compared with the conventional Cartesian acquisition, compressed sensing reconstructed rosette images provided image quality with overall higher contrast-to-noise ratio and significantly faster readout time. Accurate B 0 map estimation was achieved from the rosette acquisition with a negligible bias of 0.01 Hz between the rosette and dual-echo Cartesian gradient echo B 0 maps, using the latter as ground truth. The water-saturation spectra (Z-spectra) and amide proton transfer weighted signals obtained from the rosette-based sequence were well preserved compared with the fully sampled data, both in the phantom and human studies., Conclusions: Fast, motion-robust, and inherent B 0 -corrected CEST and magnetization transfer contrast imaging using rosette trajectories could improve subject comfort and compliance, contrast-to-noise ratio, and provide inherent B 0 homogeneity information. This work is expected to significantly accelerate the translation of CEST-MRI into a robust, clinically viable approach., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Magnetic resonance spectroscopic imaging (MRSI) provides information about the spatial distribution of metabolites in the brain. These metabolite maps can be valuable in diagnosing central nervous system pathology. However, MRSI generally suffers from a long acquisition time, poor spatial resolution, and a low metabolite signal-to-noise ratio (SNR). Ultrahigh field strengths (≥ 7 T) can benefit MRSI with an improved SNR and allow high-resolution metabolic mapping. Non-Cartesian spatial-spectral encoding techniques, such as rosette spectroscopic imaging, can efficiently sample spatial and temporal domains, which significantly reduces the imaging time and enables high-resolution metabolic mapping in a clinically relevant scan time. In the current study, high-resolution (in-plane resolution of 2 × 2 mm 2 ) mapping of proton ( 1 H) metabolites in the human brain at 7 T, is demonstrated. Five healthy subjects participated in the study. Using a time-efficient rosette trajectory and short TR/TE free induction decay MRSI, high-resolution maps of 1 H metabolites were obtained in a clinically relevant imaging time (6 min). Suppression of the water signal was achieved with an optimized water suppression enhanced through T1 effects approach and lipid removal was performed using L 2 -regularization in the postprocessing. Spatial distributions of N-acetyl-aspartate, total choline, creatine, N-acetyl-aspartyl glutamate, myo-inositol, and glutamate were generated with Cramer-Rao lower bounds of less than 20%., (© 2023 John Wiley & Sons Ltd.)

Blood-brain barrier (BBB) dysfunction is associated with a number of central nervous system diseases. This study demonstrates the application of a novel noninvasive technique to measure the BBB permeability in the human brain at 7 T. The technique exploits the fact that, when tissue macromolecules are saturated by off-resonance RF pulse, the intravascular and the extravascular (tissue) water experience different magnetization transfer effects. This principle was combined with arterial spin labeling to distinguish between the intravascular and the tissue water, and was used to calculate perfusion, water extraction fraction (E), and BBB permeability surface area product for water (PS). Simultaneous coregistered magnetization transfer ratio maps were also generated that can provide valuable additional information. Eighteen healthy volunteers (seven females), age = 27 ± 11 years and weight = 65 ± 9 kg, participated in the study. Average perfusion was 67 ± 5 and 29 ± 4 ml/100 g/min (p < 0.05); and E was 0.921 ± 0.025 and 0.962 ± 0.015 (p < 0.05) in the gray matter (GM) and the white matter (WM), respectively. PS was higher in the GM (171 ± 20 ml/100 g/min) compared with the WM (95 ± 18 ml/100 g/min) (p < 0.05). The parameters exhibited good reliability with test re-test experiments. The sensitivity of this technique was demonstrated by 200 mg caffeine intake, which resulted in a decrease in the resting PS by ~31%., (© 2023 John Wiley & Sons, Ltd.)

MRI is a valuable diagnostic tool to investigate spinal cord (SC) pathology. SC MRI can benefit from the increased signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) at ultra-high fields such as 7 T. However, SC MRI acquisitions with routine Cartesian readouts are prone to image artifacts caused by physiological motion. MRI acquisition techniques with non-Cartesian readouts such as rosette can help reduce motion artifacts. The purpose of this study was to demonstrate the feasibility of high-resolution SC imaging using rosette trajectory with magnetization transfer preparation (MT-prep) and compressed sensing (CS) at 7 T. Five healthy volunteers participated in the study. Images acquired with rosette readouts demonstrated reduced motion artifacts compared to the standard Cartesian readouts. The combination of multi-echo rosette-readout images improved the CNR by approximately 50% between the gray matter (GM) and white matter (WM) compared to single-echo images. MT-prep images showed excellent contrast between the GM and WM with magnetization transfer ratio (MTR) and cerebrospinal fluid normalized MT signal (MTCSF) = 0.12 ± 0.017 and 0.74 ± 0.013, respectively, for the GM; and 0.18 ± 0.011 and 0.58 ± 0.009, respectively, for the WM. Under-sampled acquisition using rosette readout with CS reconstruction demonstrated up to 6 times faster scans with comparable image quality as the fully-sampled acquisition., (© 2023. The Author(s).)

The purpose of the present study was to demonstrate a new sequence and determine the repeatability of simultaneous dynamic measurements of blood flow, venous oxygen saturation (SvO 2 ), and relative perfusion (change from resting perfusion) in calf muscle during recovery from plantar flexion exercise. The feasibility of near simultaneous measurement of bio-energetic parameters was also demonstrated. A sequence was developed to simultaneously measure arterial blood flow using flow-encoded projection, SvO 2 using susceptibility-based oximetry, and relative perfusion using arterial spin labeling in combination with dynamic plantar flexion exercise. The parameters were determined at rest and during recovery from single leg plantar flexion exercise. Test-retest repeatability was analyzed using Bland-Altman analysis and intraclass correlation coefficients (ICC). The mitochondrial capacity of skeletal muscle was also measured immediately afterwards with dynamic phosphorus magnetic resonance spectroscopy. Eight healthy subjects participated in the study for test-retest repeatability. Popliteal artery blood flow at rest was 1.79 ± 0.58 ml/s and increased to 11.18 ± 3.02 ml/s immediately after exercise. Popliteal vein SvO 2 decreased to 45.93% ± 6.5% from a resting value of 70.46% ± 4.76% following exercise. Relative perfusion (change from rest value) was 51.83 ± 15.00 ml/100 g/min at the cessation of exercise. The recovery of blood flow and SvO 2 was modeled as a single exponential with time constants of 38.03 ± 6.91 and 71.19 ± 14.53 s, respectively. All the measured parameters exhibited good repeatability with ICC ranging from 0.8 to 0.95. Bioenergetics measurements were within normal range, demonstrating the feasibility of near simultaneous measurement of hemodynamic and energetic parameters. Clinical feasibility was assessed with Barth syndrome patients, demonstrating reduced oxygen extraction from the blood and reduced mitochondrial oxidative capacity compared with healthy controls. The proposed protocol allows rapid imaging of multiple parameters in skeletal muscle that might be affected in disease., (© 2022 John Wiley & Sons Ltd.)

Impairments in oxygen delivery and consumption can lead to reduced muscle endurance and physical disability. Perfusion, a measure of microvascular blood flow, provides information on nutrient delivery. T 2 * provides information about relative tissue oxygenation. Changes in these parameters following stress, such as exercise, can yield important information about imbalance between delivery and consumption. In this study, we implemented novel golden angle radial MRI acquisition technique to simultaneously quantify muscle perfusion and T 2 * at 7T with improved temporal resolution, and demonstrated assessment of spatial and temporal changes in these parameters within calf muscles during recovery from plantar flexion exercise. Nine healthy subjects participated the studies. At rest, perfusion and T 2 * in gastrocnemius muscle group within calf muscle were 5 ± 2 mL/100 g/min and 21.1 ± 3 ms respectively. Then the subjects performed plantar flexion exercise producing a torque of ~8ft-lb. Immediately after the exercise, perfusion was elevated to 79.3 ± 9 mL/100 g/min and T 2 * was decreased by 6 ± 3%. The time constants for 50% perfusion and T 2 * recovery were 54.1 ± 10 s and 68.5 ± 7 s respectively. These results demonstrate successful simultaneous quantification of perfusion and T 2 * in skeletal muscle using the developed technique.

This study is a secondary data analysis from the National Health Morbidity Survey III, a population-based study conducted in 2006. A total of 7,749 children between 7 and 12 years old were recruited into the study. This study seeks to report the prevalence of overweight (including obesity) children in Malaysia using international cut-off point and identify its associated key social determinants. The results show that the overall prevalence of overweight children in Malaysia was 19.9%. The urban residents, males, Chinese, those who are wealthy, have overweight or educated guardians showed higher prevalence of overweight. In multivariable analysis, higher likelihood of being overweight was observed among those with advancing age (OR=1.15), urban residents (OR=1.16, 95% CI: 1.01-1.36), the Chinese (OR=1.45, 95% CI: 1.19-1.77), boys (OR=1.23, 95% CI: 1.08-1.41), and those who came from higher income family. In conclusion, one out of five of 7-12 year-old-children in Malaysia were overweight. Locality of residence, ethnicity, gender, guardian education, and overweight guardian were likely to be the predictors of this alarming issue. Societal and public health efforts are needed in order to reduce the burden of disease associated with obesity.

Clozapine (Clozaril) is a novel and unique prototype atypical, tricyclic, dibenzodiazepine-derivative, antipsychotic agent. It has been proven effective and significantly superior to placebo, as well as to conventional neuroleptics, in several placebo-controlled, double-blind studies in treatment-resistant schizophrenia. It has also been found to produce an incidence of extrapyramidal symptoms (EPS) as low as that found with placebo. Approximately 30-60% of all schizophrenic patients who fail to respond to typical antipsychotics may respond to clozapine. It was the first major advance that marked a turning point in the treatment of schizophrenia and other psychotic disorders since the introduction of the typical antipsychotic agents, i.e., chlorpromazine and haloperidol in the 1950s and 1960s, respectively. After its introduction in clinical studies in the United States in the early 1970s, it was withdrawn in 1974, and was not approved for clinical use in the United States until February 1990, because of the risk of agranulocytosis. Its novel pharmacological profile, lack of propensity to cause EPS in both short- and long-term uses, lack of effects on serum prolactin, and ameliorative effects on tardive dyskinesia have resulted in the expansion of its use from refractory schizophrenia to schizoaffective disorders, affective disorders, some neurological disorders, aggression, as well as psychosis in patients with dementia and parkinsonism. This review covers the history, pharmacology, management of side effects, and fetal and neonatal effects of clozapine.

Antianxiety medications such as benzodiazepines (BZDs) are frequently and appropriately used to ameliorate the anxiety symptoms of depression, dysthymic disorder, panic disorder, agoraphobia, obsessive-compulsive disorder, generalized anxiety disorder, eating disorder, and many personality disorders. Pregnancy may be accompanied by anxiety necessitating therapeutic intervention by anxiolytic drugs like BZD. Keeping in view the potential risks of teratogenicity and direct neonatal toxicity, BZDs with established safety records should be used, while avoiding exposure in the first trimester, especially with multidrug regimens, and prescribing the lowest dose for the shortest duration. This literature review highlights information from various sources regarding safety data of exposure of pregnant and lactating mothers to long-acting BZDs, especially diazepam.

The chronic, complex, and episodic course of bipolar mood disorder presents a particularly formidable challenge to the clinician making a treatment plan for the onset or recurrence of the illness during pregnancy and lactation. Women treated with anti-manic drugs who become pregnant are commonly considered to be at high risk for fetal complications during the pregnancy or during lactation. The risks of antimanic drug use during pregnancy include teratogenic effects, direct neonatal toxicity, and the potential for longer-term neurobehavioral sequela. The use of medications during pregnancy and lactation requires critical attention to the timing of exposure, dosage, duration of use, and fetal susceptibility. The postnatal period is a time of increased onset and relapse of mental illness. No antimanic drug can be proven completely safe. Prescribing antimanic medications with a long safety record, avoiding exposure in the first trimester; avoiding multidrug regimens, and prescribing the lowest dose for the shortest duration will minimize the fetal risk. This review considers treatment with lithium, valproic acid, and carbamazepine. It assesses the risk to the fetus, the perinatal risks for the infant, the risks associated with treatment during the puerperium and breast-feeding, and the risks to the later development of the child.