Intratumoral evaluation of 3D microvasculature and nanoparticle distribution using a gadolinium-dendron modified nano-liposomal contrast agent with magnetic resonance micro-imaging

The enhanced permeability and retention (EPR) effect is variable depending on nanoparticle properties and tumor/vessel conditions. Thus, intratumoral evaluations of the vasculature and nanoparticle distribution are important for predicting the therapeutic efficacy and the intractability of tumors. We aimed to develop a tumor vasculature evaluation method and high-resolution nanoparticle delivery imaging using magnetic resonance (MR) micro-imaging technology with a gadolinium (Gd)-dendron assembled liposomal contrast agent. Using the Gd-liposome and a cryogenic receiving coil, we achieved 50-μm isotropic MR angiography with clear visualization of tumor micro-vessel structure. The Gd-liposome-enhanced MR micro-imaging revealed differences in the vascular structures between Colon26- and SU-DHL6-grafted mice models. The vessel volumes and diameters measured for both tumors were significantly correlated with histological observations. The MR micro-imaging methods facilitate the evaluation of intratumoral vascularization patterns, the quantitative assessment of vascular-properties that alter tumor malignancy, particle retentivity, and the effects of treatment.     

Multi-parameter MRI to investigate vasculature modulation and photo-thermal ablation combination therapy against cancer

Nanotransducer-mediated photothermal therapy (PTT) has emerged as an attractive therapy modality against cancer, but its efficacy is often limited by the amount of nanoparticles delivered to tumors. Previous studies showed a vasculature modulation treatment, which dilates or prunes tumor blood vessels, may enhance tumor uptake of nanoparticles. However, exploiting these approaches for improved PTT has seldom been studied. In this study, we investigated the impact of mild hyperthermia or anti-angiogenesis therapy on PTT. Briefly, we gave tumor-bearing balb/c mice low doses of sunitinib or submerged tumors in a 42?°C water bath. Next, we injected PEGylated reduced graphene oxide (RGO-PEG) and irradiated the tumors to induce PTT. We then followed up the treatment with multi-parameter MRI. Contrary to expectation, both vessel modulation strategies led to diminished PTT efficacy. Our results show that vessel modulation does not warrant improved PTT, and should be carefully gauged when used in combination with PTT.     

Perfusion MR imaging at 3-Tesla: Can it predict tumor grade and histologic necrosis rate of musculoskeletal sarcoma?

Purpose

To identify quantitative perfusion parameters that are best associated with tumor grade and tumor necrosis at magnetic resonance (MR) imaging at 3-Tesla.

DWI of the spinal cord with reduced FOV single‐shot EPI

Single‐shot echo‐planar imaging (ss‐EPI) has not been used widely for diffusion‐weighted imaging (DWI) of the spinal cord, because of the magnetic field inhomogeneities around the spine, the small cross‐sectional size of the spinal cord, and the increased motion in that area due to breathing, swallowing, and cerebrospinal fluid (CSF) pulsation. These result in artifacts with the usually long readout duration of the ss‐EPI method. Reduced field‐of‐view (FOV) methods decrease the required readout duration for ss‐EPI, thereby enabling its practical application to imaging of the spine. In this work, a reduced FOV single‐shot diffusion‐weighted echo‐planar imaging (ss‐DWEPI) method is proposed, in which a 2D spatially selective echo‐planar RF excitation pulse and a 180° refocusing pulse reduce the FOV in the phase‐encode (PE) direction, while suppressing the signal from fat simultaneously. With this method, multi slice images with higher in‐plane resolutions (0.94 × 0.94 mm² for sagittal and 0.62 × 0.62 mm² for axial images) are achieved at 1.5 T, without the need for a longer readout. Magn Reson Med 60:468–473, 2008. © 2008 Wiley‐Liss, Inc.     

Sex-specific variation of MRI-based cortical morphometry in adult healthy volunteers: the effect on cognitive functioning

Previous investigations have revealed sex-specific differences in brain morphometry. The effect of sex on cortical thickness may be influencing cognitive differences between sexes. With this exploratory study, we aimed to investigate the effect of sex in MRI-based cerebral cortex morphometry in healthy young volunteers and how the variability in cortical measures might affect cognitive functioning in men and women. 76 young healthy volunteers (45 men and 31 women) underwent a 1.5 T MR scan and 53 of them completed a comprehensive cognitive battery. Overall no gross significant differences between sexes were found in cortical thickness, surface area and curvature indexes. However, there was a significant group by hemisphere interaction in the total cortical thickness (F(1,72) = 5.02; p = 0.03). A greater leftward asymmetry was observed in cortical thickness in males. Only females show significant associations between cortical thickness and cognitive functioning (IQ and executive functioning). In conclusion, our findings do not support the notion of sexual dimorphism in cortical mantle morphology. The results also suggest that variability in cortical thickness may affect cognitive functioning in females but not in males.     

Disrupted regional homogeneity in treatment-resistant depression: a resting-state fMRI study

Background

Using a newly developed regional homogeneity (ReHo) approach, we were to explore the features of brain activity in patients with treatment-resistant depression (TRD) in resting state, and further to examine the relationship between abnormal brain activity in TRD patients and specific symptom factors derived from ratings on the Hamilton Rating Scale for Depression (HRSD).

Methods

24 patients with TRD and 19 gender-, age-, and education-matched healthy subjects participated in the fMRI scans.

Results

1.

Compared with healthy controls, decreased ReHo were found in TRD patients in the left insula, superior temporal gyrus, inferior frontal gyrus, lingual gyrus and cerebellum anterior lobe (culmen) (p < 0.05, corrected).

2.

Compared with healthy controls, increased ReHo were found in the left superior temporal gyrus, cerebellum posterior lobe (tuber), cerebellum anterior lobe (culmen), the right cerebellar tonsil and bilateral fusiform gyrus (p < 0.05, corrected).

3.

There was no correlation between the ReHo values in any brain region detected in our study and the patients' age, years of education, illness duration, HRSD total score and its symptom factors.

Limitation

The influence of antidepressants to the brain activity in TRD patients was not fully eliminated.

Conclusions

The pathogenesis of TRD may be attributed to abnormal neural activity in multiple brain regions.     

Development of fetal brain of 20 weeks gestational age: assessment with post-mortem Magnetic Resonance Imaging

Background

The 20th week gestational age (GA) is at mid-gestation and corresponds to the age at which the termination of pregnancy in several countries and the first Magnetic Resonance Imaging (MRI) can be performed, and at which the premature babies may survive. However, at present, very little is known about the exact anatomical character at this GA.

Objective

To delineate the developing fetal brain of 20 weeks GA and obtain the three dimensional visualization model.

Materials and methods

20 fetal specimens were scanned by 3.0 T and 7.0 T post-mortem MRI, and the three dimensional visualization model was obtained with Amira 4.1.

Results

Most of the sulci or their anlage, except the postcentral sulcus and intraparietal sulcus, were present. The laminar organization, described as layers with different signal intensities, was most clearly distinguished at the parieto-occipital lobe and peripheral regions of the hippocampus. The basal nuclei could be clearly visualized, and the brain stem and cerebellum had formed their common shape. On the visualization model, the shape and relative relationship of the structures could be appropriately delineated. The ranges of normal values of the brain structures were obtained, but no sexual dimorphisms or cerebral asymmetries were found.

Conclusions

The developing fetal brain of 20 weeks GA can be clearly delineated on 3.0 T and 7.0 T post-mortem MRIs, and the three dimensional visualization model supplies great help in precise cognition of the immature brain. These results may have positive influences on the evaluation of the fetal brain in the uterus.     

Auditory orienting and inhibition of return in schizophrenia: A functional magnetic resonance imaging study

Patients with schizophrenia (SP) exhibit deficits in both attentional reorienting and inhibition of return (IOR) during visual tasks. However, it is currently unknown whether these deficits are supramodal in nature and how these deficits relate to other domains of cognitive dysfunction. In addition, the neuronal correlates of this pathological orienting response have not been investigated in either the visual or auditory modality. Therefore, 30 SP and 30 healthy controls (HC) were evaluated with an extensive clinical protocol and functional magnetic resonance imaging (fMRI) during an auditory cuing paradigm. SP exhibited both increased costs and delayed IOR during auditory orienting, suggesting a prolonged interval for attentional disengagement from cued locations. Moreover, a delay in the development of IOR was associated with cognitive deficits on formal neuropsychological testing in the domains of attention/inhibition and working memory. Event-related fMRI showed the characteristic activation of a frontoparietal network (invalid trials > valid trials), but there were no differences in functional activation between patients and HC during either attentional reorienting or IOR. Current results suggest that orienting deficits are supramodal in nature in SP, and are related to higher-order cognitive deficits that directly interfere with day-to-day functioning.     

Alterations of the amplitude of low-frequency fluctuations in treatment-resistant and treatment-response depression: A resting-state fMRI study

Background

Patients with treatment-resistant depression (TRD) and those with treatment-response depression (TSD) respond to antidepressants differently and previous studies have commonly reported different brain networks in resistant and nonresistant patients. Using the amplitude of low-frequency fluctuations (ALFF) approach, we explored ALFF values of the brain regions in TRD and TSD patients at resting state to test the hypothesis of the different brain networks in TRD and TSD patients.

Methods

Eighteen TRD patients, 17 TSD patients and 17 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans.

Results

There are widespread differences in ALFF values among TRD patients, TSD patients and healthy subjects throughout the cerebellum, the visual recognition circuit (middle temporal gyrus, middle/inferior occipital gyrus and fusiform), the hate circuit (putamen), the default circuit (ACC and medial frontal gyrus) and the risk/action circuit (inferior frontal gyrus). The differences in brain circuits between the TRD and TSD patients are mainly in the cerebellum, the visual recognition circuit and the default circuit.

Conclusions

The affected brain circuits of TRD patients might be partly different from those of TSD patients.