For nearly 20 years, the prevalent view has been that women who carry copies of the ε4 allele of the apolipoprotein E (APOE) gene have a greater risk of developing Alzheimer disease (AD) than men with the same number of copies.¹ The ε4 allele is the main genetic risk factor for late-onset Alzheimer disease (AD),² and sex-based differences in AD risk have important implications for treatment trials, diagnostics, and therapeutics.³ Additionally, the sex-dependent relationship between APOE and mild cognitive impairment (MCI), which is often a transitional phase from cognitively normal (NL) aging to dementia,⁴ is unclear. Studies are in general agreement that the APOE ε4 allele is a risk factor for developing MCI,^5-11 but there is controversy as to whether it increases^10,12-14 or does not increase^9,11,15,16 the risks of transitioning from MCI to AD or dementia. The 3 most common alleles of the APOE gene are ε2, ε3, and ε4; whereas carrying the ε4 allele increases one’s risk of developing AD, the ε2 allele conversely has a putative protective effect that is associated with longevity and a lower AD risk.¹⁷

Both parallel MRI and compressed sensing (CS) are emerging techniques to accelerate conventional MRI by reducing the number of acquired data. The combination of parallel MRI and CS for further acceleration is of great interest. In this paper, we propose a novel method to combine sensitivity encoding (SENSE), one of the standard methods for parallel MRI, and compressed sensing for rapid MR imaging (SparseMRI), a recently proposed method for applying CS in MR imaging with Cartesian trajectories. The proposed method, named CS‐SENSE, sequentially reconstructs a set of aliased reduced‐field‐of‐view images in each channel using SparseMRI and then reconstructs the final image from the aliased images using Cartesian SENSE. The results from simulations and phantom and in vivo experiments demonstrate that CS‐SENSE can achieve a reduction factor higher than those achieved by SparseMRI and SENSE individually and outperform the existing method that combines parallel MRI and CS. Magn Reson Med, 2009.

To demonstrate the feasibility of using focused ultrasound to enhance delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to glioblastomas in rats with induced tumors and determine if such an approach increases treatment efficacy. All animal experiments were approved by the animal committee and adhered to the experimental animal care guidelines. A 400-kHz focused ultrasound generator was used to transcranially disrupt the blood-brain barrier (BBB) in rat brains by delivering burst-tone ultrasound energy in the presence of microbubbles. The process was monitored in vivo by using magnetic resonance (MR) imaging. Cultured C6 glioma cells implanted in Sprague-Dawley rats were used as the tumor model. BCNU (13.5 mg/kg) was administered intravenously and its concentration in brains was quantified by using high-performance liquid chromatography. MR imaging was used to evaluate the effect of treatments longitudinally, including analysis of tumor progression and animal survival, and brain tissues were histologically examined. Methods including the two-tailed unpaired t test and the Mantel-Cox test were used for statistical analyses, with a significance level of .05. Focused ultrasound significantly enhanced the penetration of BCNU through the BBB in normal (by 340%) and tumor-implanted (by 202%) brains without causing hemorrhaging. Treatment of tumor-implanted rats with focused ultrasound alone had no beneficial effect on tumor progression or on animal survival up to 60 days. Administration of BCNU only transiently controlled tumor progression; nevertheless, relative to untreated controls, animal survival was improved by treatment with BCNU alone (increase in median survival time [IST(median)], 15.7%, P = .023). Treatment with focused ultrasound before BCNU administration controlled tumor progression (day 31: 0.05 cm(3) + or - 0.1 [standard deviation] vs 0.28 cm(3) + or - 0.1) and improved animal survival relative to untreated controls (IST(median), 85.9%, P = .0015). This study demonstrates a means of increasing localized chemotherapeutic drug delivery for brain tumor treatment and strongly supports the feasibility of this treatment in a clinical setting.

The superparamagnetic properties of magnetic nanoparticles (MNPs) allow them to be guided by an externally positioned magnet and also provide contrast for MRI. However, their therapeutic use in treating CNS pathologies in vivo is limited by insufficient local accumulation and retention resulting from their inability to traverse biological barriers. The combined use of focused ultrasound and magnetic targeting synergistically delivers therapeutic MNPs across the blood–brain barrier to enter the brain both passively and actively. Therapeutic MNPs were characterized and evaluated both in vitro and in vivo, and MRI was used to monitor and quantify their distribution in vivo. The technique could be used in normal brains or in those with tumors, and significantly increased the deposition of therapeutic MNPs in brains with intact or compromised blood–brain barriers. Synergistic targeting and image monitoring are powerful techniques for the delivery of macromolecular chemotherapeutic agents into the CNS under the guidance of MRI.

To examine the usefulness of diffusion kurtosis imaging for the diagnosis of Parkinson disease (PD). Examinations were performed with the understanding and written consent of each subject, with local ethics committee approval, and in compliance with national legislation and Declaration of Helsinki guidelines. Diffusion-weighted magnetic resonance imaging was performed in 30 patients with idiopathic PD (mean age, 64.5 years ± 3.4 [standard deviation]) and 30 healthy subjects (mean age, 65.0 years ± 5.1). Mean kurtosis, fractional anisotropy, and mean, axial, and radial diffusivity of the basal ganglia were compared between the groups. Disease severity was assessed by using Hoehn and Yahr staging and the motor section of the Unified Parkinson's Disease Rating Scale (mean scores, 2.0 and 33.6, respectively). Receiver operating characteristic (ROC) analysis was used to compare the diagnostic accuracies of the indexes of interest. Pearson correlation coefficient analysis was used to correlate imaging findings with disease severity. Mean kurtosis in the putamen was higher in the PD group (0.93 ± 0.15) than in the control group (0.71 ± 0.09) (P < .000416). The area under the ROC curve (AUC) was 0.95 for both the ipsilateral putamen and the ipsilateral substantia nigra. The mean kurtosis for the ipsilateral substantia nigra had the best diagnostic performance (mean cutoff, 1.10; sensitivity, 0.92; specificity, 0.87). In contrast, AUCs for the tensor-derived indexes ranged between 0.43 (axial and radial diffusivity in substantia nigra) and 0.65 (fractional anisotropy in substantia nigra). Diffusion kurtosis imaging in the basal ganglia, as compared with conventional diffusion-tensor imaging, can improve the diagnosis of PD.

Purpose: To evaluate diffusion‐weighted imaging (DWI) for detection of pelvic lymph node metastasis in patients with cervical and uterine cancers.Materials and Methods: Fifty patients scheduled for pelvic lymph node dissection were enrolled for 3T magnetic resonance imaging (MRI) using a single‐shot echo‐planar DWI technique, body‐phased array coil, b = 0, 1000 s/mm². We measured short/long‐axis diameters, mean apparent diffusion coefficient (ADC) values of all identifiable nodes, relative ADC values between tumors and nodes, and utilized their cutoff values to validate the diagnostic accuracy internally. Histopathologic results served as the reference standard.Results: The relative ADC values between tumor and nodes were significantly lower in metastatic than in benign nodes (0.06 vs. 0.21 × 10⁻³ mm²/s, P < 0.001; cutoff value 0.10 × 10⁻³ mm²/s). Compared to conventional MRI, the method combining size and relative ADC values resulted in better sensitivity (25% vs. 83%) and similar specificity (98% vs. 99%). The smallest metastatic lymph node detected by this method measured 5 mm on its short axis.Conclusion: The combination of size and relative ADC values was useful in detecting pelvic lymph node metastasis in patients with cervical and uterine cancers. J. Magn. Reson. Imaging 2008.