Hypothalamic neuronal activation in non-human primates drives naturalistic goal-directed eating behavior.

Maladaptive feeding behavior is the primary cause of modern obesity. While the causal influence of the lateral hypothalamic area (LHA) on eating behavior has been established in rodents, there is currently no primate-based evidence available on naturalistic eating behaviors. We investigated the role of LHA GABAergic (LHAGABA) neurons in eating using chemogenetics in three macaques. LHAGABA neuron activation significantly increased naturalistic goal-directed behaviors and food motivation, predominantly for palatable food. Positron emission tomography and magnetic resonance spectroscopy validated chemogenetic activation. Resting-state functional magnetic resonance imaging revealed that the functional connectivity (FC) between the LHA and frontal areas was increased, while the FC between the frontal cortices was decreased after LHAGABA neuron activation. Thus, our study elucidates the role of LHAGABA neurons in eating and obesity therapeutics for primates and humans.

Association Between Taurine Level in the Hippocampus and Major Depressive Disorder in Young Women: A Proton Magnetic Resonance Spectroscopy Study at 7T.

BACKGROUND: Major depressive disorder (MDD) is characterized by depressed mood or loss of interest or pleasure. Generally, women are twice as likely as men to have depression. Taurine, a type of amino acid, plays critical roles in neuronal generation, differentiation, arborization, and formation of synaptic connections. Importantly, it enhances proliferation and synaptogenesis in the hippocampus. When injected into animals, taurine has an antidepressant effect. However, there is no in vivo evidence to show an association between taurine concentration in the human brain and the development of MDD. METHODS: Forty-one unmedicated young women with MDD (ages 18-29) and 43 healthy control participants matched for gender and age were recruited in South Korea. Taurine concentration was measured in the hippocampus, anterior cingulate cortex, and occipital cortex of the MDD and healthy control groups using proton magnetic resonance spectroscopy at 7T. Analysis of covariance was used to examine differences in taurine concentration, adjusting for age as a covariate. RESULTS: Taurine concentration in the hippocampus was lower (F1,75 = 5.729, p = .019, Δη2 = 0.073) for the MDD group (mean [SEM] = 0.91 [0.06] mM) than for the healthy control group (1.13 [0.06] mM). There was no significant difference in taurine concentration in the anterior cingulate cortex or occipital cortex between the two groups. CONCLUSIONS: This study demonstrates that a lower level of taurine concentration in the hippocampus may be a novel characteristic of MDD.

Task-residual effective connectivity of motor network in transient ischemic attack.

Transient ischemic attack (TIA) is a temporary episode of neurological dysfunction that results from focal brain ischemia. Although TIA symptoms are quickly resolved, patients with TIA have a high risk of stroke and persistent impairments in multiple domains of cognitive and motor functions. In this study, using spectral dynamic causal modeling, we investigate the changes in task-residual effective connectivity of patients with TIA during fist-closing movements. 28 healthy participants and 15 age-matched patients with TIA undergo functional magnetic resonance imaging at 7T. Here we show that during visually cued motor movement, patients with TIA have significantly higher effective connectivity toward the ipsilateral primary motor cortex and lower connectivity to the supplementary motor area than healthy controls. Our results imply that TIA patients have aberrant connections among motor regions, and these changes may reflect the decreased efficiency of primary motor function and disrupted control of voluntary movement in patients with TIA.

Attenuated facial movement in depressed women is associated with symptom severity, and nucleus accumbens functional connectivity.

It is assumed that mood can be inferred from one's facial expression. While this association may prove to be an objective marker for mood disorders, few studies have explicitly evaluated this linkage. The facial movement responses of women with major depressive disorder (n = 66) and healthy controls (n = 46) under emotional stimuli were recorded using webcam. To boost facial movements, the naturalistic audio-visual stimuli were presented. To assess consistent global patterns across facial movements, scores for facial action units were extracted and projected onto principal component using principal component analysis. The associations of component for facial movements with functional brain circuitry was also investigated. Clusters of mouth movements, such as lip press and stretch, identified by principal component analysis, were attenuated in depressive patients compared to those in healthy controls. This component of facial movements was associated with depressive symptoms, and the strengths of resting brain functional connectivity between nucleus accumbens and both posterior insular cortex and thalamus. The evaluation of facial movements may prove to be a promising quantitative marker for assessing depressive symptoms and their underlying brain circuitry.

Genome-wide assessment reveals a significant association between ACSS3 and physical activity.

Recent genetic studies have identified physical activity (PA)-susceptible loci in European ancestry subjects; however, due to considerable genetic differences, these findings are not likely extendable to East Asian populations. Therefore, the present study aimed to identify significantly associated PA-susceptible loci using genome-wide association studies (GWASs) with East Asian (EAS) subjects and to generalize the findings to European (EUR) ancestries. The mRNA levels of genes located near the genome-wide significantly associated single-nucleotide polymorphisms (SNP) were compared under PA and control conditions. Rs74937256, located in ACSS3 (chromosome 12), which primarily functions in skeletal muscle tissues, was identified as a genome-wide significant variant (P = 6.06 × 10-9 ) in EAS. Additionally, the rs2525840, also in ACSS3 satisfied the Bonferroni corrected significance (P = 3.77 × 10-5 ) in EUR. We found that rs74937256 is an expressed trait locus of ACSS3 (P = 10-4 ), and ACSS3 mRNA expression significantly differs after PA, based on PrediXcan (P = 7 × 10-8 ) and the gene expression omnibus database (P = 0.043).

Hypoxia-Responsive Luminescent CEST MRI Agent for In Vitro and In Vivo Tumor Detection and Imaging.

Hypoxia is a feature of most solid tumors and a key determinant of cancer growth and propagation. Sensing hypoxia effectively could lead to more favorable clinical outcomes. Here, we report a molecular antenna-based bimodal probe designed to exploit the complementary advantages of magnetic resonance (MR)- and optical-based imaging. Specifically, we describe the synthesis and evaluation of a dual-action probe (NO2-Eu) that permits hypoxia-activated chemical exchange saturation transfer (CEST) MR and optical imaging. In CT26 cells, this NO2-Eu probe not only provides an enhanced CEST MRI signal but also turns "on" the optical signal under hypoxic conditions. Time-dependent in vivo CEST imaging in a hypoxic CT26 tumor xenograft mouse model revealed probe-dependent tumor detection by CEST MRI contrast in the tumor area. We thus suggest that dual-action hypoxia probes, like that reported here, could have a role to play in solid tumor diagnosis and monitoring.

Repeatable Self-Healing of a Protective Coating Based on Vegetable-Oil-Loaded Microcapsules.

Generally, microcapsule-based self-healing materials have the limitation of single local self-healing. A few studies have reported repeatable self-healing in these microcapsular materials, but there is a challenge to develop multi-cycle self-healing materials that have the advantages of easier preparation and a more efficient operation. In this work, a mixture of two vegetable oils, soybean and olive oil, was used as a healing agent. The atmospheric oxygen-induced reaction behavior (in the presence of a catalyst) was investigated for various compositions of the vegetable oil mixtures; infrared spectroscopy, recovery testing, and viscoelasticity measurement were performed to find an optimum composition of the healing agent. Microcapsules loaded with soybean oil and catalyst-containing olive oil were separately prepared and used to prepare a dual-capsule self-healing coating. It was demonstrated through optical and scanning electron microscopy that, upon scribing the self-healing coating, the vegetable oils flowed out from microcapsules to self-heal the damaged area. When the healed area of the self-healing coating was re-scribed, self-healing was repeated, which was confirmed by scanning electron microscopy (SEM) and anticorrosion and electrochemical testing. Our new repeatable self-healing coating provides the merits of easy preparation, no need for external intervention such as light irradiation, and an environmentally-friendly nature.

In vitro study on the effects of photodynamic inactivation using methyl pheophorbide a, PhotoMed, PhotoCure, and 660 nm diode laser on Candida albicans.

BACKGROUND: Candida albicans (C. albicans) is the most common fungal pathogen that causes clinical infections in humans. This study aimed to evaluate the effects of photodynamic inactivation (PDI) using a 660 nm diode laser along with methyl pheophorbide a, PhotoMed, and PhotoCure as photosensitizer for analyzing the viability of in vitro inactivation of C. albicans Methods: In the PDI group, 20 µL of C. albicans suspension and 20 µL of photosensitizer were inoculated in a 90 mm petri dish (63.6 cm2). The samples were placed in an incubator at 37 °C for 30 min, and then they were irradiated with light (660 nm diode laser, 3 J/cm2). After laser irradiation, the cells were stored for 48 h at 37 °C in an incubator with 5% CO2, and the number of colonies was counted. RESULTS: The highest reduction in the number of colony-forming units per milliliter (CFU/mL) after PDI was observed in the presence of methyl pheophorbide a and PhotoMed, followed by PhotoCure. One-way analysis of variance (ANOVA) demonstrated a significant inhibition (F = 384.717; P < 0.05) for each PDI. CONCLUSIONS: In this study, we demonstrated that the application of PDI to C. albicans using methyl pheophorbide a and PhotoMed resulted in 100% death rates. PDI could be a treatment method because conventional antifungals have limited effects, and they may not eliminate C. albicans completely.

Hyperoxia-Induced ΔR1.

Background and Purpose- Acceleration of longitudinal relaxation under hyperoxic challenge (ie, hyperoxia-induced ΔR1) indicates oxygen accumulation and reflects baseline tissue oxygenation. We evaluated the feasibility of hyperoxia-induced ΔR1 for evaluating cerebral oxygenation status and degree of ischemic damage in stroke. Methods- In 24-hour transient stroke rat models (n=13), hyperoxia-induced ΔR1, ischemic severity (apparent diffusion coefficient [ADC]), vasogenic edema (R2), total and microvascular blood volume (superparamagnetic iron oxide-driven ΔR2* and ΔR2, respectively), and glucose metabolism activity (18F-fluorodeoxyglucose uptake on positron emission tomography) were measured. The distribution of these parameters according to hyperoxia-induced ΔR1 was analyzed. The partial pressure of tissue oxygen change during hyperoxic challenge was measured using fiberoptic tissue oximetry. In 4-hour stroke models (n=6), ADC and hyperoxia-induced ΔR1 was analyzed with 2,3,5-triphenyltetrazolium chloride staining being a criterion of infarction. Results- Ischemic hemisphere showed significantly higher hyperoxia-induced ΔR1 than nonischemic brain in a pattern depending on ADC. During hyperoxic challenge, ischemic hemisphere demonstrated uncontrolled increase of partial pressure of tissue oxygen, whereas contralateral hemisphere rapidly plateaued. Ischemic hemisphere also demonstrated significant correlation between hyperoxia-induced ΔR1 and R2. Hyperoxia-induced ΔR1 showed a significant negative correlation with 18F-fluorodeoxyglucose uptake. The ADC, R2, ΔR2, and 18F-fluorodeoxyglucose uptake showed a dichotomized distribution according to the hyperoxia-induced ΔR1 as their slopes and values were higher at low hyperoxia-induced ΔR1 (<50 ms-1) than at high ΔR1. In 4-hour stroke rats, the distribution of ADC according to the hyperoxia-induced ΔR1 was similar with 24-hour stroke rats. The hyperoxia-induced ΔR1 was greater in the infarct area (47±10 ms-1) than in peri-infarct area (16±4 ms-1; P<0.01). Conclusions- Hyperoxia-induced ΔR1 adequately indicates cerebral oxygenation and can be a feasible biomarker to classify the degree of ischemia-induced damage in neurovascular function and metabolism in stroke brain.

The Effect on Bone Outcomes of Home-based Exercise Intervention for Prostate Cancer Survivors Receiving Androgen Deprivation Therapy: A Pilot Randomized Controlled Trial.

BACKGROUND: Cancer treatment-induced bone loss has important long-term effects in prostate cancer survivors (PCSs) receiving androgen deprivation therapy (ADT), but little is known about preventive interventions. OBJECTIVE: The aim of this study was to examine the feasibility and preliminary effectiveness of a 6-month home-based exercise intervention in PCSs. METHODS: In this pilot, randomized controlled trial, 51 men (mean age, 70.8 years) were randomized to a 6-month home-based exercise intervention for preventing osteoporosis group (n = 26) or an exercise placebo intervention of stretching exercise group (n = 25). Primary outcomes were bone mineral density and bone turnover markers. Secondary outcomes were physical performance (level of physical activity, muscle strength, and balance) and health-related quality of life. RESULTS: The patient retention rate for 6 months was 80.4%. The mean adherence rate was 84.7% for weight-bearing exercise and 64.8% for resistance exercise. No adverse events during the study period were reported. Although primary outcomes did not differ significantly between the 2 groups, the home-based exercise intervention for preventing osteoporosis group demonstrated significantly greater increased muscle strength than the stretching exercise group. CONCLUSIONS: A home-based exercise program is relatively feasible and safe and may improve muscle strength but not bone outcomes. IMPLICATIONS FOR PRACTICE: Given the importance of preventing cancer treatment-induced bone loss among PCSs receiving ADT, a home-based exercise intervention can be considered, but further trials with a larger sample are required to determine its effect for bone outcomes.

The Neuromelanin-related T2* Contrast in Postmortem Human Substantia Nigra with 7T MRI.

High field magnetic resonance imaging (MRI)-based delineation of the substantia nigra (SN) and visualization of its inner cellular organization are promising methods for the evaluation of morphological changes associated with neurodegenerative diseases; however, corresponding MR contrasts must be matched and validated with quantitative histological information. Slices from two postmortem SN samples were imaged with a 7 Tesla (7T) MRI with T1 and T2* imaging protocols and then stained with Perl's Prussian blue, Kluver-Barrera, tyrosine hydroxylase, and calbindin immunohistochemistry in a serial manner. The association between T2* values and quantitative histology was investigated with a co-registration method that accounts for histology slice preparation. The ventral T2* hypointense layers between the SNr and the crus cerebri extended anteriorly to the posterior part of the crus cerebri, which demonstrates the difficulty with an MRI-based delineation of the SN. We found that the paramagnetic hypointense areas within the dorsolateral SN corresponded to clusters of neuromelanin (NM). These NM-rich zones were distinct from the hypointense ventromedial regions with high iron pigments. Nigral T2* imaging at 7T can reflect the density of NM-containing neurons as the metal-bound NM macromolecules may decrease T2* values and cause hypointense signalling in T2* imaging at 7T.

Bone health and its correlates in Korean prostate cancer patients receiving androgen deprivation therapy.

PURPOSE: This study aimed to examine bone health status, identify factors associated with bone mineral density (BMD), and determine potential risk factors for osteoporosis in Korean prostate cancer patients receiving androgen deprivation therapy (ADT). METHODS: Using a cross-sectional descriptive design, we recruited 139 men with prostate cancer receiving ADT at two university-based hospitals in South Korea. Participants completed a self-reported questionnaire and underwent dual energy X-ray absorptiometry testing. BMD (gm/cm(2)), bone health status (normal BMD, osteopenia, and osteoporosis), and lifestyle variables (physical activity, smoking, and alcohol consumption) were measured. RESULTS: The prevalence in our sample was 49.6% for osteopenia and 17.3% for osteoporosis. In multivariate linear regression analyses, BMD was positively associated with body mass index, number of comorbidities, and level of physical activity and negatively associated with being unemployed or retired, having a lower monthly income, and being treated with gonadotropin-releasing hormone therapy alone. In logistic regression analyses, potential risk factors for osteoporosis were low monthly income (OR = 4.33, p = 0.011), receipt of radiation therapy (OR = 4.69, p = 0.018), and lack of regular physical activity (OR = 2.63, p = 0.035). CONCLUSIONS: Our results suggest that a proportion of prostate cancer survivors who are receiving ADT warrant monitoring to prevent osteoporosis, particularly men of lower economic status and those having lower levels of physical activity. Nurses can play an important role in screening these high risk groups.

Lumazine Synthase Protein Nanoparticle-Gd(III)-DOTA Conjugate as a T1 contrast agent for high-field MRI.

With the applications of magnetic resonance imaging (MRI) at higher magnetic fields increasing, there is demand for MRI contrast agents with improved relaxivity at higher magnetic fields. Macromolecule-based contrast agents, such as protein-based ones, are known to yield significantly higher r1 relaxivity at low fields, but tend to lose this merit when used as T1 contrast agents (r1/r2 = 0.5 ~ 1), with their r1 decreasing and r2 increasing as magnetic field strength increases. Here, we developed and characterized an in vivo applicable magnetic resonance (MR) positive contrast agent by conjugating Gd(III)-chelating agent complexes to lumazine synthase isolated from Aquifex aeolicus (AaLS). The r1 relaxivity of Gd(III)-DOTA-AaLS-R108C was 16.49 mM(-1)s(-1) and its r1/r2 ratio was 0.52 at the magnetic field strength of 7 T. The results of 3D MR angiography demonstrated the feasibility of vasculature imaging within 2 h of intravenous injection of the agent and a significant reduction in T1 values were observed in the tumor region 7 h post-injection in the SCC-7 flank tumor model. Our findings suggest that Gd(III)-DOTA-AaLS-R108C could serve as a potential theranostic nanoplatform at high magnetic field strength.

Oxygen-induced frequency shifts in hyperoxia: a significant component of BOLD signal.

In comparison to the well-documented significance of intravascular deoxyhemoglobin (deoxyHgb), the effects of dissolved oxygen on the blood-oxygen-level-dependent (BOLD) signal have not been widely reported. Based on the fact that the prolonged inspiration of high oxygen fraction gas can result in up to a sixfold increase of the baseline tissue oxygenation, the current study focused on the influence of dissolved oxygen on the BOLD signal during hyperoxia. As results, our in vitro study revealed that the r1 and r2 (relaxivities) of the oxygen-treated serum were 0.22 mM(-1) · s(-1) and 0.19 mM(-1) · s(-1) , respectively. In an in vivo experiment, hyperoxic respiration induced negative BOLD contrast (i.e. signal decrease) in 18-42% of measured brain regions, voxels with accompanying significant decreases in both the T(*)2 (-12.1% to -19.4%) and T1 (-5.8% to -3.3%) relaxation times. In contrast, the T(*)2 relaxation time significantly increased (11.2% to 14.0%) for the voxels displaying positive BOLD contrast (in 41-50% of the measured brain), which reflected a hyperoxygenation-induced reduction in tissue deoxyHgb concentration. These data imply that hyperoxia-driven BOLD signal changes are primarily determined by the counteracting effects of extravascular oxygen and intravascular deoxyHgb. Oxygen-induced magnetic susceptibility was further demonstrated by the study of 1 min hypoxia, which induced BOLD signal changes opposite to those under hyperoxia. Vasoconstriction was more common in voxels with negative BOLD contrast than in voxels with positive contrast (% change of blood volume, -9.8% to -12.8% versus 2.0% to 2.2%), which further suggests that negative BOLD contrast is mainly evoked by an increase in extravascular oxygen concentration. Conclusively, frequency shifts, which are induced by the accumulation of oxygen molecules and associated magnetic field inhomogeneity, are a significant source of the negative BOLD contrast during hyperoxia.

Response of the primary auditory and non-auditory cortices to acoustic stimulation: a manganese-enhanced MRI study.

Structural and functional features of various cerebral cortices have been extensively explored in neuroscience research. We used manganese-enhanced MRI, a non-invasive method for examining stimulus-dependent activity in the whole brain, to investigate the activity in the layers of primary cortices and sensory, such as auditory and olfactory, pathways under acoustic stimulation. Male Sprague-Dawley rats, either with or without exposure to auditory stimulation, were scanned before and 24-29 hour after systemic MnCl2 injection. Cortex linearization and layer-dependent signal extraction were subsequently performed for detecting layer-specific cortical activity. We found stimulus-dependent activity in the deep layers of the primary auditory cortex and the auditory pathways. The primary sensory and visual cortices also showed the enhanced activity, whereas the olfactory pathways did not. Further, we performed correlation analysis of the signal intensity ratios among different layers of each cortex, and compared the strength of correlations between with and without the auditory stimulation. In the primary auditory cortex, the correlation strength between left and right hemisphere showed a slight but not significant increase with the acoustic simulation, whereas, in the primary sensory and visual cortex, the correlation coefficients were significantly smaller. These results suggest the possibility that even though the primary auditory, sensory, and visual cortices showed enhanced activity to the auditory stimulation, these cortices had different associations for auditory processing in the brain network.

Sunitinib--CLIO conjugate: a VEGFR/PDGFR-targeting active MR probe.

PURPOSE: This study was conducted to evaluate feasibility of sunitinib-CLIO conjugate as a vascular endothelial growth factor receptor/platelet-derived growth factor receptor (VEGFR/PDGFR)-specific magnetic resonance (MR) probe. PROCEDURE: VEGFR/PDGFR-targeting MR probe was synthesized by conjugating cross-linked iron-oxide (CLIO) with tyrosine-kinase inhibitor (sunitinib). In VEGFR/PDGFR-positive (U118MG) and VEGFR/PDGFR-negative (HT29) cells and tumor models, conjugate-driven ΔR 2 was estimated, while CLIO was used as control. Prussian-blue staining was performed for quantifying the amount of tumor-binding conjugates. RESULTS: ΔR 2 between sunitinib-CLIO-treated and non-treated cells was greater in U118MG (mean, 2.1/s) than in HT29 cells (1.0/s). In in vivo study, conjugate induced a greater ΔR 2 in U118MG (11.2/s) than HT29 tumors (5.9/s). Conjugate-induced R 2 changes were not correlated with degree of Gd-DTPA enhancement, demonstrating that tumor binding of sunitinib-CLIO was independent of enhanced permeability and retention effect. % area of Prussian-blue staining was greater in U118MG (8.5 %) than in HT29 (1.4 %). CONCLUSIONS: Sunitinib-CLIO conjugate can be used as an active MR probe for quantifying VEGFR/PDGFR.

Dynamic contrast-enhanced MRI for monitoring antiangiogenic treatment: determination of accurate and reliable perfusion parameters in a longitudinal study of a mouse xenograft model.

OBJECTIVE: To determine the reliable perfusion parameters in dynamic contrast-enhanced MRI (DCE-MRI) for the monitoring antiangiogenic treatment in mice. MATERIALS AND METHODS: Mice, with U-118 MG tumor, were treated with either saline (n = 3) or antiangiogenic agent (sunitinib, n = 8). Before (day 0) and after (days 2, 8, 15, 25) treatment, DCE examinations using correlations of perfusion parameters (Kep, Kel, and A(H) from two compartment model; time to peak, initial slope and % enhancement from time-intensity curve analysis) were evaluated. RESULTS: Tumor growth rate was found to be 129% ± 28 in control group, -33% ± 11 in four mice with sunitinib-treatment (tumor regression) and 47% ± 15 in four with sunitinib-treatment (growth retardation). Kep (r = 0.80) and initial slope (r = 0.84) showed strong positive correlation to the initial tumor volume (p < 0.05). In control mice, tumor regression group and growth retardation group animals, Kep (r : 0.75, 0.78, 0.81, 0.69) and initial slope (r : 0.79, 0.65, 0.67, 0.84) showed significant correlation with tumor volume (p < 0.01). In four mice with tumor re-growth, Kep and initial slope increased 20% or greater at earlier (n = 2) than or same periods (n = 2) to when the tumor started to re-grow with 20% or greater growth rate. CONCLUSION: Kep and initial slope may a reliable parameters for monitoring the response of antiangiogenic treatment.

Sunlight-induced self-healing of a microcapsule-type protective coating.

Photopolymerization behavior of a methacryloxypropyl-terminated polydimethylsiloxane (MAT-PDMS) healing agent was investigated in the presence of benzoin isobutyl ether (BIE) photoinitiator by Fourier transform infrared (FT-IR) spectroscopy. MAT-PDMS and BIE were microencapsulated with urea-formaldehyde polymer. The surface and shell morphology of the microcapsules was investigated by scanning electron microscopy (SEM). Mean diameter and size distribution of the microcapsules could be controlled by agitation rate. A coating matrix formulation was prepared by sol-gel reaction of tetraethyl orthosilicate (TEOS) in the presence of a polysiloxane and by subsequent addition of an adhesion promoter. The formulation and microcapsules were mixed to give a self-healing coating formulation, which was then sprayed to surface of cellulose-fiber-reinforced-cement (CRC) board or mortar. Contact angle measurements showed that both the polymerized MAT-PDMS and the prepared coating matrix are hydrophobic, and the coating matrix has good wettability with MAT-PDMS. It was confirmed by optical microscopy and SEM that, when the self-healing coating is damaged, the healing agent is released from ruptured microcapsules and fills the damaged region. The self-healing coating was evaluated as protective coating for mortar, and it was demonstrated by water permeability and chloride ion penetration tests that our system has sunlight-induced self-healing capability. Our self-healing coating is the first example of capsule-type photoinduced self-healing system, and offers the advantages of catalyst-free, environmentally friendly, inexpensive, practical healing.

Temporal/spatial resolution improvement of in vivo DCE-MRI with compressed sensing-optimized FLASH.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides critical information regarding tumor perfusion and permeability by injecting a T(1) contrast agent, such as Gd-DTPA, and making a time-resolved measurement of signal increase. Both temporal and spatial resolutions are required to be high to achieve an accurate and reproducible estimation of tumor perfusion. However, the dynamic nature of the DCE experiment limits simultaneous improvement of temporal and spatial resolution by conventional methods. Compressed sensing (CS) has become an important tool for the acceleration of imaging times in MRI, which is achieved by enabling the reconstruction of subsampled data. Similarly, CS algorithms can be utilized to improve the temporal/spatial resolution of DCE-MRI, and several works describing retrospective simulations have demonstrated the feasibility of such improvements. In this study, the fast low angle shot sequence was modified to implement a Cartesian, CS-optimized, sub-Nyquist phase encoding acquisition/reconstruction with multiple two-dimensional slice selections and was tested on water phantoms and animal tumor models. The mean voxel-level concordance correlation coefficient for Ak(ep) values obtained from ×4 and ×8 accelerated and the fully sampled data was 0.87±0.11 and 0.83±0.11, respectively (n=6), with optimized CS parameters. In this case, the reduction of phase encoding steps made possible by CS reconstruction improved effectively the temporal/spatial resolution of DCE-MRI data using an in vivo animal tumor model (n=6) and may be useful for the investigation of accelerated acquisitions in preclinical and clinical DCE-MRI trials.

Is apparent diffusion coefficient reliable and accurate for monitoring effects of antiangiogenic treatment in a longitudinal study?

PURPOSE: To evaluate the reliability and accuracy of the apparent diffusion coefficient (ADC) for monitoring antiangiogenic treatment in a longitudinal study. MATERIALS AND METHODS: Tumor volume and ADC were monitored by T2-weighted magnetic resonance imaging (MRI) and diffusion-weighted MRI, respectively, in 18 mice with angiogenesis-dependent tumors (U118MG) before (day 0) and after 2, 7, 14, and 21 days of administration of the antiangiogenic agent sunitinib maleate (n = 12) or vehicle (n = 6). Percent changes in tumor volume and ADC were calculated and correlations between tumor volume and ADC were evaluated. RESULTS: Tumor volume and ADC showed a negative correlation at 69 of the 72 (96%) follow-up measurements. In the 13 mice with tumor regrowth, ADC started to decrease before (27%) or at the same time (73%) as tumor regrowth. Pretreatment ADC and percent change in ADC change on days 0-2 were similar in mice with positive and negative responses to treatment (0.851 vs. 0.999, 24% vs. 16%). Percent change of ADC showed significant negative correlation with percent change in tumor volume in both the control (r = -0.69) and treated (r = -0.65) groups. CONCLUSION: Percent change in ADC is a reliable and accurate marker for monitoring the effects of antiangiogenic treatment, whereas pretreatment ADC and early changes in ADC (ie, days 0-2) are limited in predicting treatment outcome.