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1.
Cancer Med ; 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31389669

RESUMO

BACKGROUND: T1-weighted dynamic contrast-enhanced (DCE) perfusion magnetic resonance imaging (MRI) has been broadly utilized in the evaluation of brain tumors. We aimed at assessing the diagnostic accuracy of DCE-MRI in discriminating between low-grade gliomas (LGGs) and high-grade gliomas (HGGs), between tumor recurrence and treatment-related changes, and between primary central nervous system lymphomas (PCNSLs) and HGGs. METHODS: We performed this study based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis of Diagnostic Test Accuracy Studies criteria. We systematically surveyed studies evaluating the diagnostic accuracy of DCE-MRI for the aforementioned entities. Meta-analysis was conducted with the use of a random effects model. RESULTS: Twenty-seven studies were included after screening of 2945 possible entries. We categorized the eligible studies into three groups: those utilizing DCE-MRI to differentiate between HGGs and LGGs (14 studies, 546 patients), between recurrence and treatment-related changes (9 studies, 298 patients) and between PCNSLs and HGGs (5 studies, 224 patients). The pooled sensitivity, specificity, and area under the curve for differentiating HGGs from LGGs were 0.93, 0.90, and 0.96, for differentiating tumor relapse from treatment-related changes were 0.88, 0.86, and 0.89, and for differentiating PCNSLs from HGGs were 0.78, 0.81, and 0.86, respectively. CONCLUSIONS: Dynamic contrast-enhanced-Magnetic resonance imaging is a promising noninvasive imaging method that has moderate or high accuracy in stratifying gliomas. DCE-MRI shows high diagnostic accuracy in discriminating between HGGs and their low-grade counterparts, and moderate diagnostic accuracy in discriminating recurrent lesions and treatment-related changes as well as PCNSLs and HGGs.

2.
J Phys Chem B ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31449408

RESUMO

Exogenous chemical exchange saturation transfer (CEST) contrast agents such as glucose or 2-deoxy-d-glucose (2-DG) have shown high sensitivities and significant potential for monitoring glucose uptake in tumors with MRI. Here, we show that liposome encapsulation of such agents can be exploited to enhance the CEST signal by reducing the overall apparent exchange rate. We have developed a concise analytical model to describe the liposomal contrast dependence on several parameters such as pH, temperature, irradiation amplitude, and intraliposomal water content. This is the first study in which a model has been constructed to measure the exchange properties of diamagnetic CEST agents encapsulated inside liposomes. Experimentally measured exchange rates of glucose and 2-DG in the liposomal system were found to be reduced due to the intermembrane exchange between the intra- and extraliposomal compartments because of restrictions in water transfer imposed by the lipid membrane. These new theoretical and experimental findings will benefit applications of diamagnetic liposomes to image biological processes. In addition, combining this analytical model with measurements of the CEST signal enhancement using liposomes as a model membrane system is an important new general technique for studying membrane permeability.

3.
Pediatr Res ; 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31357208

RESUMO

BACKGROUND: Neuroprotection from therapeutic hypothermia (HT) is incomplete, therefore additional strategies are necessary to improve long-term outcomes. We assessed the neuroprotective efficacy of magnesium sulfate (MgSO4) bolus and infusion over 48 h plus HT in a piglet model of term neonatal encephalopathy (NE). METHODS: Fifteen newborn piglets were randomized following hypoxia-ischemia (HI) to: (i) MgSO4 180 mg/kg bolus and 8 mg/kg/h infusion with HT (Mg+HT) or (ii) HT and saline 0.5 ml/h (HT). Treatments were initiated 1 h post-HI; HT administered for 12 h (33.5 °C). HI was performed by transient carotid occlusion and inhalation of 6% O2 for 20-25 min. Primary outcomes included aEEG, magnetic resonance spectroscopy (MRS) at 24, and 48 h, and immunohistochemistry. RESULTS: MgSO4 bolus and infusion was well tolerated (no hypotension) and doubled serum magnesium (0.72 vs 1.52 mmol/L) with modest (16%) rise in CSF. In Mg+HT compared to HT, there was overall reduced cell death (p = 0.01) and increased oligodendrocytes (p = 0.002). No improvement was seen on aEEG recovery (p = 0.084) or MRS (Lac/NAA; PCr/Pi; NTP/epp) (p > 0.05) at 48 h. CONCLUSION: Doubling serum magnesium with HT was safe; however, the small incremental benefit of Mg+HT compared to HT is unlikely to translate into substantive long-term improvement. Such an incremental effect might justify further study of MgSO4 in combination with multiple therapies.

4.
NMR Biomed ; 32(9): e4113, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31313865

RESUMO

AIMS: To determine individual glucose hydroxyl exchange rates at physiological conditions and use this information for numerical optimization of glucoCEST/CESL preparation. To give guidelines for in vivo glucoCEST/CESL measurement parameters at clinical and ultra-high field strengths. METHODS: Five glucose solution samples at different pH values were measured at 14.1 T at various B1 power levels. Multi-B1 -Z-spectra Bloch-McConnell fits at physiological pH were further improved by the fitting of Z-spectra of five pH values simultaneously. The obtained exchange rates were used in a six-pool Bloch-McConnell simulation including a tissue-like water pool and semi-solid MT pool with different CEST and CESL presaturation pulse trains. In vivo glucose injection experiments were performed in a tumor mouse model at 7 T. RESULTS AND DISCUSSION: Glucose Z-spectra could be fitted with four exchanging pools at 0.66, 1.28, 2.08 and 2.88 ppm. Corresponding hydroxyl exchange rates could be determined at pH = 7.2, T = 37°C and 1X PBS. Simulation of saturation transfer for this glucose system in a gray matter-like and a tumor-like system revealed optimal pulses at different field strengths of 9.4, 7 and 3 T. Different existing sequences and approaches are simulated and discussed. The optima found could be experimentally verified in an animal model at 7 T. CONCLUSION: For the determined fast exchange regime, presaturation pulses in the spin-lock regime (long recover time, short yet strong saturation) were found to be optimal. This study gives an estimation for optimization of the glucoCEST signal in vivo on the basis of glucose exchange rate at physiological conditions.

5.
Sci Rep ; 9(1): 10184, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31308390

RESUMO

Co-existing infection/inflammation and birth asphyxia potentiate the risk of developing neonatal encephalopathy (NE) and adverse outcome. In a newborn piglet model we assessed the effect of E. coli lipopolysaccharide (LPS) infusion started 4 h prior to and continued for 48 h after hypoxia on brain cell death and systemic haematological changes compared to LPS and hypoxia alone. LPS sensitized hypoxia resulted in an increase in mortality and in brain cell death (TUNEL positive cells) throughout the whole brain, and in the internal capsule, periventricular white matter and sensorimotor cortex. LPS alone did not increase brain cell death at 48 h, despite evidence of neuroinflammation, including the greatest increases in microglial proliferation, reactive astrocytosis and cleavage of caspase-3. LPS exposure caused splenic hypertrophy and platelet count suppression. The combination of LPS and hypoxia resulted in the highest and most sustained systemic white cell count increase. These findings highlight the significant contribution of acute inflammation sensitization prior to an asphyxial insult on NE illness severity.

6.
J Neurol Neurosurg Psychiatry ; 90(7): 755-760, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30948625

RESUMO

OBJECTIVE: Sodium (23Na)-MRI is an emerging imaging technique to investigate in vivo changes in tissue viability, reflecting neuroaxonal integrity and metabolism. Using an optimised 23Na-MRI protocol with smaller voxel sizes and improved tissue contrast, we wanted to investigate whether brain total sodium concentration (TSC) is a biomarker for long-term disease outcomes in a cohort of patients with relapse-onset multiple sclerosis (MS), followed from disease onset. METHODS: We performed a cross-sectional study in 96 patients followed up ~ 15 years after a clinically isolated syndrome (CIS) and 34 healthy controls. Disease course was classified as CIS, relapsing-remitting MS or secondary progressive MS (SPMS). We acquired 1H-MRI and 23Na-MRI and calculated the TSC in cortical grey matter (CGM), deep grey matter, normal-appearing white matter (WM) and WM lesions. Multivariable linear regression was used to identify independent associations of tissue-specific TSC with physical disability and cognition, with adjustment for tissue volumes. RESULTS: TSC in all tissues was higher in patients with MS compared with healthy controls and patients who remained CIS, with differences driven by patients with SPMS. Higher CGM TSC was independently associated with Expanded Disability Status Scale (R2=0.26), timed 25-foot walk test (R2=0.23), 9-hole peg test (R2=0.23), Paced Auditory Serial Addition Test (R2=0.29), Symbol Digit Modalities Test (R2=0.31) and executive function (R2=0.36) test scores, independent of grey matter atrophy. CONCLUSIONS: Sodium accumulation in CGM reflects underlying neuroaxonal metabolic abnormalities relevant to disease course heterogeneity and disability in relapse-onset MS. TSC and should be considered as an outcome measure in future neuroprotection trials.

7.
Magn Reson Imaging ; 59: 61-67, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30802487

RESUMO

Pseudo-continuous arterial spin labelling (pCASL) is the MRI method of choice for non-invasive perfusion measurement in research and clinical practice. Knowledge of the labelling efficiency, α, is essential for accurate quantification of cerebral blood flow (CBF). Typically, a theoretical α value is used, based on an idealistic model and an assumption of spins flowing perpendicularly to the labelling plane. The aim of this work was to investigate the effect of violating this assumption, and to characterize the influence of labelling plane angulation with respect to the vessel direction on labelling efficiency and measured CBF. The effect of labelling plane angulation on labelling efficiency was demonstrated using a numerical simulation of spins at different velocities. Acquisitions from healthy volunteers were used to test the effect of a range of angulation offsets. Additional sub-optimal positions of the labelling plane with respect to the vertebral arteries, at locations where the direction of flow changes significantly from the head-foot direction, were also considered. No significant change in the measured CBF was seen when the labelling plane was angled up to 60° to the labelled vessel or when it was placed in sub-optimal positions. This study shows that in adult subjects, the efficiency of pCASL is robust to the angulation and positioning of the labelling plane beyond the range of potential operator error.


Assuntos
Artérias/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo/fisiologia , Circulação Cerebrovascular/fisiologia , Angiografia por Ressonância Magnética , Marcadores de Spin , Adulto , Feminino , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Reprodutibilidade dos Testes
8.
J Magn Reson Imaging ; 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770603

RESUMO

BACKGROUND: Chemical exchange saturation transfer (CEST) can potentially support cancer imaging with metabolically derived information. Multiparametric prostate MRI has improved diagnosis but may benefit from additional information to reduce the need for biopsies. PURPOSE: To optimize an acquisition and postprocessing protocol for 3.0 T multipool CEST analysis of prostate data and evaluate the repeatability of the technique. STUDY TYPE: Prospective. SUBJECTS: Five healthy volunteers (age range: 24-47 years; median age: 28 years) underwent two sessions (interval range: 7-27 days; median interval: 20 days) and two biopsy-proven prostate cancer patients were evaluated once. Patient 1 (71 years) had a Gleason 3 + 4 transition zone (TZ) tumor and patient 2 (55 years) had a Gleason 4 + 3 peripheral zone (PZ) tumor. FIELD STRENGTH: 3.0 T. Sequences run: T2 -weighted turbo-spin-echo (TSE); diffusion-weighted imaging; CEST; WASABI (for B0 determination). ASSESSMENT: Saturation, readout, and fit-model parameters were optimized to maximize in vivo amide and nuclear Overhauser effect (NOE) signals. Repeatability (intrasession and intersession) was evaluated in healthy volunteers. Subsequently, preliminary evaluation of signal differences was made in patients. Regions of interest were drawn by two post-FRCR board-certified readers, both with over 5 years of experience in multiparametric prostate MRI. STATISTICAL TESTS: Repeatability was assessed using Bland-Altman analysis, coefficient of variation (CV), and 95% limits of agreement (LOA). Statistical significance of CEST contrast was calculated using a nonparametric Mann-Whitney U-test. RESULTS: The optimized saturation scheme was found to be 60 sinc-Gaussian pulses with 40 msec pulse duration, at 50% duty-cycle with continuous-wave pulse equivalent B1 power (B1CWPE ) of 0.92 µT. The magnetization transfer (MT) contribution to the fit-model was centered at -1.27 ppm. Intersession coefficients of variation (CVs) of the amide, NOE, and magnetization transfer (MT) and asymmetric magnetization transfer ratio (MTRasym ) signals of 25%, 23%, 18%, and 200%, respectively, were observed. Fit-metric and MTRasym CVs agreed between readers to within 4 and 10 percentage points, respectively. DATA CONCLUSION: Signal differences of 0.03-0.10 (17-43%) detectable depending upon pool, with MT the most repeatable (signal difference of 17-22% detectable). LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019.

9.
J Magn Reson ; 300: 120-134, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30739012

RESUMO

Fitting a model based on the Bloch-McConnell (BM) equations to Chemical Exchange Saturation Transfer (CEST) spectra allows for the quantification of metabolite concentration and exchange rate as well as simultaneous correction of field inhomogeneity, direct water saturation and magnetization transfer. Employing a Bayesian fitting approach permits the integration of prior information into the analysis to incorporate expected parameter distributions and to prevent over-fitting. However, the analysis can be time consuming if a general numerical solution of the BM equations is applied. In this study, we combined a Bayesian fitting algorithm with approximate analytical solutions of the BM equations to achieve feasible computational times. To evaluate the accuracy and speed of the suggested approach, phantoms including Iodipamide, Taurine and Creatine were tested in addition to simulated data with continuous-wave (CW) and pulsed saturation with Gaussian pulses. A significant reduction of computational time was achieved when fitting CW data (about 50-fold) and pulsed saturation data (more than 100-fold) with the analytical model while the estimated parameters were largely consistent with the parameters from the general numerical solution. The increased speed of the algorithm facilitates the Bayesian analysis of CEST data within clinically feasible processing times. Other analytical models valid for different parameter regimes may be employed to extend the applicability to a wider range of CEST agents.

10.
AIDS Res Hum Retroviruses ; 35(5): 453-460, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30667282

RESUMO

We assessed whether HIV status was associated with white matter hyperintensities (WMH), a neuroimaging correlate of cerebral small vessel disease (CSVD), in men aged ≥50 years. A cross-sectional substudy was nested within a larger cohort study. Virologically suppressed men living with HIV (MLWH) and demographically matched HIV-negative men aged ≥50 underwent magnetic resonance imaging (MRI) at 3 Tesla. Sequences included volumetric three-dimensional (3D) T1-weighted, fluid-attenuated inversion recovery and pseudocontinuous arterial spin labeling. Regional segmentation by automated image processing algorithms was used to extract WMH volume (WMHV) and resting cerebral blood flow (CBF). The association between HIV status and WMHV as a proportion of intracranial volume (ICV; log-transformed) was estimated using a multivariable linear regression model. Thirty-eight MLWH [median age 59 years (interquartile range, IQR 55-64)] and 37 HIV-negative [median 58 years (54-63)] men were analyzed. MLWH had median CD4+ count 570 (470-700) cells/µL and a median time since diagnosis of 20 (14-24) years. Framingham 10-year risk of cardiovascular disease was 6.5% in MLWH and 7.4% in controls. Two (5%) MLWH reported a history of stroke or transient ischemic attack and five (13%) reported coronary heart disease compared with none of the controls. The total WMHV in MLWH was 1,696 µL (IQR 1,229-3,268 µL) or 0.10% of ICV compared with 1,627 µL (IQR 1,032-3,077 µL), also 0.10% of ICV in the HIV-negative group (p = .43). In the multivariable model, WMHV/ICV was not associated with HIV status (p = .86). There was an age-dependent decline in cortical CBF [-3.9 mL/100 mL/min per decade of life (95% confidence interval 1.1-6.7 mL)] but no association between CBF and HIV status (p > .2 in all brain regions analyzed). In conclusion, we found no quantitative MRI evidence of an increased burden of CSVD in MLWH aged 50 years and older.

11.
Neurobiol Dis ; 121: 240-251, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30300675

RESUMO

Therapeutic hypothermia is only partially protective for neonatal encephalopathy; there is an urgent need to develop treatments that augment cooling. Our objective was to assess safety, efficacy and pharmacokinetics of 5 and 15 mg/kg/24 h melatonin (proprietary formulation) administered at 2 h and 26 h after hypoxia-ischemia (HI) with cooling in a piglet model. Following moderate cerebral HI, 30 piglets were eligible and randomized to: i) Hypothermia (33.5 °C, 2-26 h) and vehicle (HT + V;n = 13); b) HT and 5 mg/kg melatonin over 6 h at 2 h and 26 h after HI (HT + Mel-5;n = 4); c) HT and 15 mg/kg melatonin over 6 h at 2 h and 26 h after HI (HT + Mel-15;n = 13). Intensive care was maintained for 48 h; brain MRS was acquired and cell death (TUNEL) evaluated at 48 h. Comparing HT + V with HT + Mel-5 and HT + Mel-15, there was no difference in blood pressure or inotropic support needed, brain Lactate/N Acetylaspartate at 24 h and 48 h was similar, ATP/phosphate pool was higher for HT + Mel-15 versus HT + V at 24 h (p = 0.038) but not 48 h. A localized reduction in TUNEL positive cell death was observed in the sensorimotor cortex in the 15 mg/kg melatonin group (HT + Mel-15 versus HT + V; p < 0.003) but not in the 5 mg/kg melatonin group (HT + Mel-5 versus HT + V; p = 0.808). Putative therapeutic melatonin levels were reached 8 h after HI (104 increase from baseline; ~15-30 mg/l). Mean ±â€¯SD peak plasma melatonin levels after the first infusion were 0.0014 ±â€¯0.0012 mg/l in the HT + V group, 3.97 ±â€¯1.53 mg/l in the HT + Mel-5 group and 16.8 ±â€¯8.3 mg/l in the HT + Mel-15 group. Protection was dose dependent; 15 mg/kg melatonin started 2 h after HI, given over 6 h, was well tolerated and augmented hypothermic protection in sensorimotor cortex. Earlier attainment of therapeutic plasma melatonin levels may optimize protection by targeting initial events of reperfusion injury. The time window for intervention with melatonin, as adjunct therapy with cooling, is likely to be narrow and should be considered in designing future clinical studies.

12.
J Magn Reson ; 298: 16-22, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30500568

RESUMO

PURPOSE: Dynamic CEST studies such as dynamic glucose enhanced imaging, have gained a lot of attention recently. The expected CEST effects after injection are rather small in tissue especially at clinical field strengths (0.5-2%). Small movements during the dynamic CEST measurement together with a subtraction-based evaluation can lead to pseudo CEST effects of the same order of magnitude. These artifacts are studied herein. METHODS: A brain tumor patient 3D-CEST baseline scan without glucose injection performed at 3 T is used to generate a virtual dynamic measurement introducing different kinds of simulated motion and B0 shifts. RESULTS: Minor motion (0.6 mm translations) and B0 artifacts (7 Hz shift) can lead to pseudo effects in the order of 1% in dynamic CEST imaging. Especially around tissue interfaces such as CSF borders or tumor affected areas, the pseudo effect patterns are non-intuitive and can be mistaken as dynamic agent uptake. CONCLUSION: Correction or mitigation for small motions is crucial for dynamic CEST imaging, especially in subjects with lesions. Concomitant B0 alterations can as well induce pseudo CEST effects at 3 T.

14.
Front Neurosci ; 12: 810, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30473659

RESUMO

Brain function has been investigated via the blood oxygenation level dependent (BOLD) effect using magnetic resonance imaging (MRI) for the past decades. Advances in sodium imaging offer the unique chance to access signal changes directly linked to sodium ions (23Na) flux across the cell membrane, which generates action potentials, hence signal transmission in the brain. During this process 23Na transiently accumulates in the intracellular space. Here we show that quantitative functional sodium imaging (fNaI) at 3T is potentially sensitive to 23Na concentration changes during finger tapping, which can be quantified in gray and white matter regions key to motor function. For the first time, we measured a 23Na concentration change of 0.54 mmol/l in the ipsilateral cerebellum, 0.46 mmol/l in the contralateral primary motor cortex (M1), 0.27 mmol/l in the corpus callosum and -11 mmol/l in the ipsilateral M1, suggesting that fNaI is sensitive to distributed functional alterations. Open issues persist on the role of the glymphatic system in maintaining 23Na homeostasis, the role of excitation and inhibition as well as volume distributions during neuronal activity. Haemodynamic and physiological signal recordings coupled to realistic models of tissue function will be critical to understand the mechanisms of such changes and contribute to meeting the overarching challenge of measuring neuronal activity in vivo.

15.
Artigo em Inglês | MEDLINE | ID: mdl-30322975

RESUMO

OBJECTIVE: Brain proton (1H) magnetic resonance spectroscopy (MRS) lactate/N-acetylaspartate (Lac/NAA) peak area ratio is used for prognostication in neonatal encephalopathy (NE). At 3 Tesla in NE babies, the objectives were to assess: (1) sensitivity and specificity of basal ganglia and thalamus (BGT) 1H MRS Lac/NAA for the prediction of Bayley III outcomes at 2 years using optimised metabolite fitting (Tarquin) with threonine and total NAA; (2) prediction of motor outcome with diffusion-weighted MRI; (3) BGT Lac/NAA correlation with the National Institute of Child Health and Human Development (NICHD) MRI score. SUBJECTS AND METHODS: 55 (16 inborn, 39 outborn) infants at 39w+5 d (35w+5d-42w+0d) with NE admitted between February 2012 and August 2014 to University College London Hospitals for therapeutic hypothermia underwent MRI and 1H MRS at 3T on day 2-14 (median day 5). MRIs were scored. Bayley III was assessed at 24 (22-26) months. RESULTS: 16 babies died (1 inborn, 15 outborn); 20, 19 and 21 babies had poor motor, cognitive and language outcomes. Using a threshold of 0.39, sensitivity and specificity of BGT Lac/NAA for 2-year motor outcome was 100% and 97%, cognition 90% and 97% and language 81% and 97%, respectively. Sensitivity and specificity for motor outcome of mean diffusivity (threshold 0.001 mm2/s) up to day 9 was 72% and 100% and fractional anisotropy (threshold 0.198) was 39% and 94%, respectively. Lac/NAA correlated with BGT injury on NICHD scores (2A, 2B, 3). CONCLUSION: BGT Lac/NAA on 1H MRS at 3T within 14 days accurately predicts 2-year motor, cognitive and language outcome and may be a marker directing decisions for therapies after cooling.

16.
Sci Rep ; 8(1): 15068, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305717

RESUMO

Proteasome inhibitors (PIs) are now standard of care for several cancers, and noninvasive biomarkers of treatment response are critically required for early patient stratification and treatment personalization. The present study evaluated whether chemical exchange (CEST) magnetic resonance imaging (MRI) can provide measurements that can be used as the noninvasive biomarkers of proteasome inhibition, alongside diffusion MRI and relaxometry. The sensitivity of human colorectal carcinoma cells to the PI Ixazomib was assessed via in vitro and in vivo dose-response experiments. Acute in vivo response to Ixazomib was assessed at three dosing concentrations, using CEST MRI (amide, amine, hydroxyl signals), diffusion MRI (ADC) and relaxometry (T1, T2). These responses were further evaluated with the known histological markers for Ixazomib and Bradford assay ex vivo. The CEST signal from amides and amines increased in proportion to Ixazomib dose in colorectal cancer xenografts. The cell lines differed in their sensitivity to Ixazomib, which was reflected in the MRI measurements. A mild stimulation in tumor growth was observed at low Ixazomib doses. Our results identify CEST MRI as a promising method for safely and noninvasively monitoring disrupted tumor protein homeostasis induced by proteasome inhibitor treatment, and for stratifying sensitivity between tumor types.

17.
Clin Infect Dis ; 2018 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-30084882

RESUMO

Background: Protease inhibitor monotherapy (PIM) for HIV may exert suboptimal viral control in the central nervous system. We determined whether cerebral blood flow (CBF) and regional brain volumes were associated with PIM, and whether specific cognitive domains were associated with imaging biomarkers. Methods: Cognitive assessment and brain MRI were performed after the final visit of a randomized HIV treatment strategy trial. Participants were virologically suppressed on triple therapy at trial entry and followed for 3-5 years. Thirty-seven patients randomized to ongoing triple therapy and thirty-nine randomized to PIM were studied. Resting CBF and normalized volumes were calculated for brain regions of interest, and correlated with treatment strategy and neuropsychological performance. Results: Mean age was 48.1 years (standard deviation 8.6 years), 63 were male (83%) and 64 were white (84%). Participants had median 8.1 years (interquartile range 6.4, 10.8) of antiretroviral therapy experience and CD4+ counts of median 640 cells/mm3 (interquartile range 490, 780). We found no difference between the two treatment arms in CBF or regional volumes. Regardless of treatment arm, poorer fine motor performance correlated with lower CBF in the caudate nucleus (p=0.01), thalamus (p=0.04), frontal cortex (p=0.01), occipital cortex (p=0.004) and cingulate cortex (p=0.02), and was associated with smaller supratentorial white matter volume (decrease of 0.16 in Z-score per -1% of total intracranial volume, 95% confidence interval 0.02-0.29, p=0.023). Conclusions: PIM does not confer additional risk of neurological injury compared with triple therapy. There were correlations between fine motor impairment, grey matter hypoperfusion and white matter volume loss.

18.
Nephrol Dial Transplant ; 33(suppl_2): ii4-ii14, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30137584

RESUMO

Functional renal magnetic resonance imaging (MRI) has seen a number of recent advances, and techniques are now available that can generate quantitative imaging biomarkers with the potential to improve the management of kidney disease. Such biomarkers are sensitive to changes in renal blood flow, tissue perfusion, oxygenation and microstructure (including inflammation and fibrosis), processes that are important in a range of renal diseases including chronic kidney disease. However, several challenges remain to move these techniques towards clinical adoption, from technical validation through biological and clinical validation, to demonstration of cost-effectiveness and regulatory qualification. To address these challenges, the European Cooperation in Science and Technology Action PARENCHIMA was initiated in early 2017. PARENCHIMA is a multidisciplinary pan-European network with an overarching aim of eliminating the main barriers to the broader evaluation, commercial exploitation and clinical use of renal MRI biomarkers. This position paper lays out PARENCHIMA's vision on key clinical questions that MRI must address to become more widely used in patients with kidney disease, first within research settings and ultimately in clinical practice. We then present a series of practical recommendations to accelerate the study and translation of these techniques.

19.
Contrast Media Mol Imaging ; 2018: 5360375, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29853806

RESUMO

Arterial spin labelling (ASL) allows absolute quantification of CBF via a diffusible intrinsic tracer (magnetically labelled blood water) that disperses from the vascular system into neighbouring tissue. Thus, it can provide absolute CBF quantification, which eliminates the need for the contrast agent, and can be performed repeatedly. This review will focus on the common ASL acquisition techniques (continuous, pulsed, and pseudocontinuous ASL) and how ASL image quality might be affected by intrinsic factors that may bias the CBF measurements. We also provide suggestions to mitigate these risks, model appropriately the acquired signal, increase the image quality, and hence estimate the reliability of the CBF, which consists an important noninvasive biomarker. Emerging methodologies for extraction of new ASL-based biomarkers, such as arterial arrival time (AAT) and arterial blood volume (aBV), will be also briefly discussed.

20.
Neurology ; 90(16): e1379-e1385, 2018 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-29661900

RESUMO

OBJECTIVE: To assess resting cerebral blood flow (CBF) in the whole-brain and cerebral white matter (WM) and gray matter (GM) of adults with Fabry disease (FD), using arterial spin labeling (ASL) MRI, and to investigate CBF correlations with WM hyperintensity (WMH) volume and the circulating biomarker lyso-Gb3. METHODS: This cross-sectional, case-control study included 25 patients with genetically confirmed FD and 18 age-matched healthy controls. We quantified resting CBF using Quantitative Signal Targeting With Alternating Radiofrequency Labeling of Arterial Regions (QUASAR) ASL MRI. We measured WMH volume using semiautomated software. We measured CBF in regions of interest in whole-brain, WM, and deep GM, and assessed correlations with WMH volume and plasma lyso-Gb3. RESULTS: The mean age (% male) for FD and healthy controls was 42.2 years (44%) and 37.1 years (50%). Mean whole-brain CBF was 27.56 mL/100 mL/min (95% confidence interval [CI] 23.78-31.34) for FD vs 22.39 mL/100 mL/min (95% CI 20.08-24.70) for healthy controls, p = 0.03. In WM, CBF was higher in FD (22.42 mL/100 mL/min [95% CI 17.72-27.12] vs 16.25 mL/100 mL/min [95% CI 14.03-18.48], p = 0.05). In deep GM, CBF was similar between groups (40.41 mL/100 mL/min [95% CI 36.85-43.97] for FD vs 37.46 mL/100 mL/min [95% CI 32.57-42.35], p = 0.38). In patients with FD with WMH (n = 20), whole-brain CBF correlated with WMH volume (r = 0.59, p = 0.006), not with plasma lyso-Gb3. CONCLUSION: In FD, resting CBF is increased in WM but not deep GM. In FD, CBF correlates with WMH, suggesting that cerebral perfusion changes might contribute to, or result from, WM injury.

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