Quantitative Sodium (23Na) MRI in Pediatric Gliomas: Initial Experience.

Background: 23Na MRI correlates with tumor proliferation, and studies in pediatric patients are lacking. The purpose of the study: (1) to compare total sodium concentration (TSC) between pediatric glioma and non-neoplastic brain tissue using 23Na MRI; (2) compare tissue conspicuity of bound sodium concentration (BSC) using 23Na MRI dual echo relative to TSC imaging. Methods: TSC was measured in: (1) non-neoplastic brain tissues and (2) three types of manually segmented gliomas (diffuse intrinsic brainstem glioma (DIPG), recurrent supratentorial low-grade glioma (LGG), and high-grade glioma (HGG)). In a subset of patients, serial changes in both TSC and BSC (dual echo 23Na MRI) were assessed. Results: Twenty-six pediatric patients with gliomas (median age of 12.0 years, range 4.9−23.3 years) were scanned with 23Na MRI. DIPG treated with RT demonstrated higher TSC values than the uninvolved infratentorial tissues (p < 0.001). Recurrent supratentorial LGG and HGG exhibited higher TSC values than the uninvolved white matter (WM) and gray matter (GM) (p < 0.002 for LGG, and p < 0.02 for HGG). The dual echo 23Na MRI suppressed the sodium signal within both CSF and necrotic foci. Conclusion: Quantitative 23Na MRI of pediatric gliomas demonstrates a range of values that are higher than non-neoplastic tissues. Dual echo 23Na MRI of BCS improves tissue conspicuity relative to TSC imaging.

The choice of dissection or preservation of the inferior pulmonary ligament after an upper lobectomy: a systematic review and meta-analysis.

BACKGROUND: The necessity of the inferior pulmonary ligament (IPL) dissection after an upper lobectomy remains controversial. This meta-analysis aimed to evaluate whether this accessional procedure could reduce the postoperative complications and improve outcomes. METHODS: PubMed, Embase, Ovid, Cochrane Library, CBM, and CNKI databases were searched for the relevant studies which compared the dissection with preservation of IPL during the upper lobectomy. The Review Manager 5.3 software was used for this meta-analysis. RESULTS: Three RCTs and five CCTs were included in this meta-analysis. These studies contained a total of 610 patients, in which 315 patients received a pulmonary ligament dissection (group D) after the upper lobectomy, while the other 295 patients preserved the pulmonary ligament (group P). No significant difference was demonstrated between the group D and group P in terms of drainage time after surgery (MD 0.14, 95%CI - 0.05 to 0.33, P = 0.15), rate of postoperative dead space (OR 1.33, 95%CI 0.72 to 2.46, P = 0.36), rate of postoperative complications (OR 1.20, 95%CI 0.66 to 2.19, P = 0.56). However, the pooled comparison revealed a greater change of the right main bronchial angle (MD 5.00, 95%CI 1.68 to 8.33, P = 0.003) in group D compared with group P, indicated that the dissection of IPL may lead to a greater distortion of bronchus. CONCLUSIONS: This meta-analysis confirmed that the dissection of IPL do not effectively reduce the postoperative complications and improve the prognosis. Therefore, it is not necessary to dissect the IPL after an upper lobectomy.

[18F]ML-10 PET: Initial Experience in Glioblastoma Multiforme Therapy Response Assessment.

The ability to assess tumor apoptotic response to therapy could provide a direct and prompt measure of therapeutic efficacy. 18F-labeled 2-(5-fluoro-pentyl)-2-methyl-malonic acid ([18F]ML-10) is proposed as a positron emission tomography (PET) apoptosis imaging radiotracer. This manuscript presents initial experience using [18F]ML-10 PET to predict therapeutic response in 4 patients with human glioblastoma multiforme. Each patient underwent [18F]ML-10 PET and contrast-enhanced magnetic resonance imaging (MRI) before (baseline) and at ∼2-3 weeks after therapy (early-therapy assessment). All PET and MRI data were acquired using a Siemens BioGraph mMR integrated PET/MRI scanner. PET acquisitions commenced 120 minutes after injection with 10 mCi of [18F]ML-10. Changes in [18F]ML-10 standard uptake values were assessed in conjunction with MRI changes. Time-to-progression was used as the outcome measure. One patient, ML-10 #4, underwent additional sodium-23 (23Na) MRI at baseline and early-therapy assessment. Siemens 3 T Magnetom Tim Trio scanner with a dual-tuned (1H-23Na) head coil was used for 23Na-MRI, acquiring two three-dimensional single-quantum sodium images at two echo times (TE). Volume-fraction-weighted bound sodium concentration was quantified through pixel-by-pixel subtraction of the two single-quantum sodium images. In the cases presented, [18F]ML-10 uptake changes were not clearly related to time-to-progression. We suggest that this may be because the tumors are undergoing varying rates of cell death and growth. Acquisition of complementary measures of tumor cell proliferation or viability may aid in the interpretation of PET apoptosis imaging.

Short-T2 imaging for quantifying concentration of sodium (23 Na) of bi-exponential T2 relaxation.

PURPOSE: This work intends to demonstrate a new method for quantifying concentration of sodium (23 Na) of bi-exponential T2 relaxation in patients on MRI scanners at 3.0 Tesla. THEORY AND METHODS: Two single-quantum (SQ) sodium images acquired at very-short and short echo times (TE = 0.5 and 5.0 ms) are subtracted to produce an image of the short-T2 component of the bi-exponential (or bound) sodium. An integrated calibration on the SQ and short-T2 images quantifies both total and bound sodium concentrations. Numerical models were used to evaluate signal response of the proposed method to the short-T2 components. MRI scans on agar phantoms and brain tumor patients were performed to assess accuracy and performance of the proposed method, in comparison with a conventional method of triple-quantum filtering. RESULTS: A good linear relation (R2 = 0.98) was attained between the short-T2 image intensity and concentration of bound sodium. A reduced total scan time of 22 min was achieved under the SAR restriction for human studies in quantifying both total and bound sodium concentrations. CONCLUSION: The proposed method is feasible for quantifying bound sodium concentration in routine clinical settings at 3.0 Tesla. Magn Reson Med 74:162-174, 2015. © 2014 Wiley Periodicals, Inc.

Challenges and Approaches to Quantitative Therapy Response Assessment in Glioblastoma Multiforme Using the Novel Apoptosis Positron Emission Tomography Tracer F-18 ML-10.

Evaluation of cancer-therapy efficacy at early time points is necessary for realizing the goal of delivering maximally effective treatment. Molecular imaging with carefully selected tracers and methodologies can provide the means for realizing this ability. Many therapies are aimed at inducing apoptosis in malignant tissue; thus, the ability to quantify apoptosis in vivo may be a fruitful approach. Apoptosis rate changes occur on a fast time scale, potentially allowing correspondingly rapid decisions regarding therapy value. However, quantification of tissue status based on apoptosis imaging is complicated by this time scale and by the spatial heterogeneity of the process. Using the positron emission tomography (PET) tracer 2-(5-fluoro-pentyl)-2-methyl-malonic acid (F-18 ML-10), we present methods of voxelwise analysis yielding quantitative measures of apoptosis changes, parametric apoptosis change images, and graphical representation of apoptotic features. A method of deformable registration to account for anatomic changes between scan time points is also demonstrated. Overall apoptotic rates deduced from imaging depend on tumor density and the specific rate of apoptosis, a situation resulting in an ambiguity in the source of observed image-based changes. The ambiguity may be resolved through multimodality imaging. An example of intracellular sodium magnetic resonance imaging coupled with F-18 ML-10 PET is provided.

Superparamagnetic iron oxide is suitable to label tendon stem cells and track them in vivo with MR imaging.

Tendon stem cells (TSCs) may be used to effectively repair or regenerate injured tendons. However, the fates of TSCs once implanted in vivo remain unclear. This study was aimed to determine the feasibility of labeling TSCs with super-paramagnetic iron oxide (SPIO) nano-particles to track TSCs in vivo using MRI. Rabbit TSCs were labeled by incubation with 50 µg/mL SPIO. Labeling efficiency, cell viability, and proliferation were then measured, and the stemness of TSCs was tested by quantitative real time RT-PCR (qRT-PCR) and immunocytochemistry. We found that the labeling efficiency of TSCs reached as high as 98%, and that labeling at 50 µg/mL SPIO concentrations did not alter cell viability and cell proliferation compared to non-labeled control cells. Moreover, the expression levels of stem cell markers (Nucleostemin, Nanog, and Oct-4) did not change in SPIO-labeled TSCs compared to non-labeled cells. Both labeled and non-labeled cells also exhibited similar differentiation potential. Finally, labeled TSCs could be detected by MRI both in vitro and in vivo. Taken together, the findings of this study show that labeling TSCs with SPIO particles is a feasible approach to track TSCs in vivo by MRI, which offers a non-invasive method to monitor repair of injured tendons.