Mapping mean axon diameter and intra-axonal volume fraction may have significant clinical potential because nerve conduction velocity is directly dependent on axon diameter, and several neurodegenerative diseases affect axons of specific sizes and alter axon counts. Diffusion-weighted MRI methods based on the pulsed gradient spin echo (PGSE) sequence have been reported to be able to assess axon diameter and volume fraction non-invasively. However, due to the relatively long diffusion times used, e.g. > 20 ms, the sensitivity to small axons (diameter < 2 µm) is low, and the derived mean axon diameter has been reported to be overestimated. In the current study, oscillating gradient spin echo (OGSE) diffusion sequences with variable frequency gradients were used to assess rat spinal white matter tracts with relatively short effective diffusion times (1 – 5 ms). In contrast to previous PGSE-based methods, the extra-axonal diffusion cannot be modeled as hindered (Gaussian) diffusion when short diffusion times are used. Appropriate frequency-dependent rates are therefore incorporated into our analysis and validated by histology-based computer simulation of water diffusion. OGSE data were analyzed to derive mean axon diameters and intra-axonal volume fractions of rat spinal white matter tracts (mean axon diameter ~ 1.27 – 5.54 µm). The estimated values were in good agreement with histology, including the small axon diameters (< 2.5 µm). This study establishes a framework for quantification of nerve morphology using the OGSE method with high sensitivity to small axons.

BACKGROUND This study aimed to determine the relative effect of Internet and Internet plus telephone treatment for smoking cessation on smoking abstinence among US adults. A priori hypotheses were that Internet enhanced with tailored content and social support would outperform basic Internet (BI) and that enhanced Internet (EI) plus proactive telephone counseling would outperform the other conditions. METHODS The Quit Using Internet and Telephone Treatment (iQUITT) study used a 3-group randomized controlled design comparing BI, EI, and EI and telephone combined (EI+P). The trial was conducted from March 8, 2005, through November 30, 2008. Current adult smokers in the United States who smoked 5 or more cigarettes per day were recruited via search engines. Characteristics of the 2005 participants include mean (SD) age of 35.9 (10.8) years, 51.1% women, and 86.5% white. The follow-up assessment rate at 18 months was 68.2%. The main outcome measure was 30-day point prevalence abstinence measured at 3, 6, 12, and 18 months after randomization using intent-to-treat analysis. RESULTS At 18 months, the 30-day multiple point prevalence abstinence rate across all follow-up intervals was 3.5% (BI), 4.5% (EI), and 7.7% (EI+P), with EI+P significantly outperforming BI and EI. At 18 months, 30-day single point prevalence abstinence rates were 19.0% (BI), 17.4% (EI), and 19.6% (EI+P) and did not differ among the groups. CONCLUSIONS Combined internet and telephone treatment outperforms static and dynamic Internet interventions. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00282009

Objectives To determine if combined measurements from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and diffusion weighted MRI (DW-MRI), obtained before and after the first cycle of neoadjuvant chemotherapy (NAC), are superior to single parameter measurements for predicting pathological complete response (pCR) in breast cancer patients. Materials and Methods Patients with Stage II/III breast cancer were enrolled in an IRB-approved study in which 3T DCE- and DW-MRI data were acquired before (n = 37) and after one cycle (n = 33) of NAC. Estimates of Ktrans, ve, vp, and kep (= Ktrans/ve) were generated from the DCE-MRI data using the Extended Tofts-Kety (ETK) model. The apparent diffusion coefficient (ADC) was estimated from the DW-MRI data. The derived parameter kep/ADC was compared to single parameter measurements for its ability to predict pCR after the first cycle of NAC. Results kep/ADC after the first cycle of NAC discriminated patients who went on to achieve a pCR (P < 0.001), and achieved a sensitivity, specificity, positive predictive value, and area under the receiver operator curve (AUC) of 0.92, 0.75, 0.69, and 0.86, respectively. These values were superior to the single parameters kep (AUC = 0.77) and ADC (AUC = 0.81). The AUCs between kep/ADC and kep were significantly different based on the bootstrapped 95% CIs (0.0062, 0.20), while the AUCs between kep/ADC and ADC trended towards significance (−0.12, 0.24). Conclusions A combined analysis of DCE-MRI and DW-MRI parameters was superior to single-parameter measurements for predicting pCR after the first cycle of NAC.

Purpose Cell size is a fundamental characteristic of all tissues, and changes in cell size in cancer reflect tumor status and response to treatments, such as apoptosis and cell‐cycle arrest. Unfortunately, cell size can currently be obtained only by pathological evaluation of tumor tissue samples obtained invasively. Previous imaging approaches are limited to preclinical MRI scanners or require relatively long acquisition times that are impractical for clinical imaging. There is a need to develop cell‐size imaging for clinical applications. Methods We propose a clinically feasible IMPULSED (imaging microstructural parameters using limited spectrally edited diffusion) approach that can characterize mean cell sizes in solid tumors. We report the use of a combination of pulse sequences, using different gradient waveforms implemented on clinical MRI scanners and analytical equations based on these waveforms to analyze diffusion‐weighted MRI signals and derive specific microstructural parameters such as cell size. We also describe comprehensive validations of this approach using computer simulations, cell experiments in vitro, and animal experiments in vivo and demonstrate applications in preoperative breast cancer patients. Results With fast acquisitions (~7 minutes), IMPULSED can provide high‐resolution (1.3 mm in‐plane) mapping of mean cell size of human tumors in vivo on clinical 3T MRI scanners. All validations suggest that IMPULSED provides accurate and reliable measurements of mean cell size. Conclusion The proposed IMPULSED method can assess cell‐size variations in tumors of breast cancer patients, which may have the potential to assess early response to neoadjuvant therapy.

Background and PurposeClinically, Parkinson's disease (PD) presents with asymmetric motor symptoms. The left nigrostriatal system appears more susceptible to early degeneration than the right, and a left‐lateralized pattern of early neuropathological changes is also described in several neurodegenerative conditions, including Alzheimer's disease, frontotemporal dementia, and Huntington's disease. In this study, we evaluated hemispheric differences in estimated rates of atrophy in a large, well‐characterized cohort of PD patients.MethodsOur cohort included 205 PD patients who underwent clinical assessments and T1‐weighted brain MRI's. Patients were classified into Early (n = 109) and Late stage (n = 96) based on disease duration, defined as greater than or less than 10 years of motor symptoms. Cortical thickness was determined using FreeSurfer, and a bootstrapped linear regression model was used to estimate differences in rates of atrophy between Early and Late patients.ResultsOur results show that patients classified as Early stage exhibit a greater estimated rate of cortical atrophy in left frontal regions, especially the left insula and olfactory sulcus. This pattern was replicated in left‐handed patients, and was not influenced by the degree of motor symptom asymmetry (i.e., left‐sided predominant motor symptoms). Patients classified as Late stage exhibited greater atrophy in the bilateral occipital, and right hemisphere‐predominant cortical areas.ConclusionsWe show that cortical degeneration in PD differs between cerebral hemispheres, and findings suggest a pattern of early left, and late right hemisphere with posterior cortical atrophy. Further investigation is warranted to elucidate the underlying mechanisms of this asymmetry and pathologic implications.