Analysis of parametric histogram from dynamic contrast‐enhanced MRI: application in evaluating brain tumor response to radiotherapy

Dynamic contrast‐enhanced MRI (DCE MRI) has been used to study tumor response to treatment for many years. In this study, the modified full width at half‐maximum (mFWHM), calculated from the wash‐in slope histogram, is proposed as a parameter for the evaluation of changes in tumor heterogeneity which respond to radiotherapy. Twenty‐five patients with brain tumors were evaluated and divided into the nonresponder group (n = 11) and the responder group (n = 14) according to the Response Evaluation Criteria in Solid Tumors (RECIST). All selected tumors were evaluated by mFWHM ratios of post‐ to pre‐therapy (the ratio was defined as the therapeutic mFWHM ratio, TMR). The changes in kurtosis of the histograms and the averaged K^trans within a tumor were also calculated for comparison. The receiver operating characteristic analysis and Kaplan–Meier curves were used to examine the diagnosis ability. The TMR values were significantly higher in nonresponders than in responders (p < 0.001). When compared with the other two parameters, the proposed method also demonstrated better sensitivity and specificity. When adopting the TMR for the estimation of prognosis after therapy, there was a significant difference between the population survival curves. In conclusion, the derived mFWHM reflects tumor heterogeneity, and the ability to depict patient survival probability from TMR corresponds well with that from RECIST. The results reveal that, in brain tumors, progression may be exhibited not only by tumor size, but also by tumor heterogeneity. Copyright © 2012 John Wiley & Sons, Ltd.     

Targeting cancer by binding iron: Dissecting cellular signaling pathways

Newer and more potent therapies are urgently needed to effectively treat advanced cancers that have developed resistance and metastasized. One such strategy is to target cancer cell iron metabolism, which is altered compared to normal cells and may facilitate their rapid proliferation. This is supported by studies reporting the anti-neoplastic activities of the clinically available iron chelators, desferrioxamine and deferasirox. More recently, ligands of the di-2-pyridylketone thiosemicarbazone (DpT) class have demonstrated potent and selective anti-proliferative activity across multiple cancer-types in vivo, fueling studies aimed at dissecting their molecular mechanisms of action. In the past five years alone, significant advances have been made in understanding how chelators not only modulate cellular iron metabolism, but also multiple signaling pathways implicated in tumor progression and metastasis. Herein, we discuss recent research on the targeting of iron in cancer cells, with a focus on the novel and potent DpT ligands. Several key studies have revealed that iron chelation can target the AKT, ERK, JNK, p38, STAT3, TGF-β, Wnt and autophagic pathways to subsequently inhibit cellular proliferation, the epithelial-mesenchymal transition (EMT) and metastasis. These developments emphasize that these novel therapies could be utilized clinically to effectively target cancer.     

Long-Term Outcome and Prognostic Factors After Spontaneous Cerebellar Hemorrhage

Cerebellar hemorrhage is the least common type of intracranial hemorrhage (ICH) encountered in clinical practice, and clinical data concerning the long-term outcomes are limited. This study aimed to investigate the long-term outcomes following spontaneous cerebellar hemorrhage in a cohort of Chinese patients. This single-center observational study was carried out between 1996 and 2010 and included 72 consecutive Chinese patients with a first spontaneous cerebellar hemorrhage. Of 440 patients with primary ICH, 72 (16.4%) had primary cerebellar hemorrhage. The mean age was 67.5?±?12.3?years and patients were predominantly male (54%). The 30-day mortality was 16.7% with Glasgow coma scale ??8 as the only predictor. At 6?months, 56.7% of patients who survived the first 30?days had a persistently poor functional status with modified Rankin scale score >2. After a mean follow-up of 4.7?years, 3.3% of patients had recurrent ICH, a recurrence rate of 7.3 per 1,000 patient-years. Ischemic stroke occurred in 12% of patients, an incidence of 25.5 per 1,000 patient-years. This study provided data on the long-term outcome of post-cerebellar hemorrhage in Chinese patients.     

Automated whole‐brain N‐acetylaspartate proton MRS quantification

Concentration of the neuronal marker, N‐acetylaspartate (NAA), a quantitative metric for the health and density of neurons, is currently obtained by integration of the manually defined peak in whole‐head proton (¹H)‐MRS. Our goal was to develop a full spectral modeling approach for the automatic estimation of the whole‐brain NAA concentration (WBNAA) and to compare the performance of this approach with a manual frequency‐range peak integration approach previously employed. MRI and whole‐head ¹H‐MRS from 18 healthy young adults were examined. Non‐localized, whole‐head ¹H‐MRS obtained at 3 T yielded the NAA peak area through both manually defined frequency‐range integration and the new, full spectral simulation. The NAA peak area was converted into an absolute amount with phantom replacement and normalized for brain volume (segmented from T₁‐weighted MRI) to yield WBNAA. A paired‐sample t test was used to compare the means of the WBNAA paradigms and a likelihood ratio test used to compare their coefficients of variation. While the between‐subject WBNAA means were nearly identical (12.8 ± 2.5 mm for integration, 12.8 ± 1.4 mm for spectral modeling), the latter's standard deviation was significantly smaller (by ~50%, p = 0.026). The within‐subject variability was 11.7% (±1.3 mm ) for integration versus 7.0% (±0.8 mm ) for spectral modeling, i.e., a 40% improvement. The (quantifiable) quality of the modeling approach was high, as reflected by Cramer–Rao lower bounds below 0.1% and vanishingly small (experimental ‐ fitted) residuals. Modeling of the whole‐head ¹H‐MRS increases WBNAA quantification reliability by reducing its variability, its susceptibility to operator bias and baseline roll, and by providing quality‐control feedback. Together, these enhance the usefulness of the technique for monitoring the diffuse progression and treatment response of neurological disorders. Copyright © 2014 John Wiley & Sons, Ltd.     

Temporal stability of urinary cadmium in samples collected several years apart in a population of older persons

Objectives

There is growing evidence that urine cadmium is a temporally stable biomarker indicative of long-term cadmium exposure; however questions remain with regard to generalizability to older persons, the impact of changes in smoking behavior, and the degree of temporal stability when repeat sample collection spans years instead of weeks or months.

Effect of ethnicity on disease activity and physical function in psoriatic arthritis in a multiethnic Asian population

Geographic differences in manifestation of psoriatic arthritis (PsA) could be related to differences in genetic or environmental factors. We aimed to compare the disease activity and functional status using validated outcome measures among patients with PsA of different ethnicities living in the same environment. We performed a cross-sectional study on consecutive patients with PsA classified by the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria from a single center. Sociodemographic data, clinical variables, and patient-reported outcomes were collected using a standardized protocol. Disease activities were assessed by validated composite scores: clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), Composite Psoriatic Disease Activity Index (CPDAI), and minimal disease activity (MDA). Physical function was assessed with Health Assessment Questionnaire (HAQ) and the Medical Outcome Study Short-Form 36 (SF36) physical function subscales. Linear regression analyses were performed to identify variables associated with disease activities and physical function. Ninety-eight patients (51.5%, men) with mean (±SD) age and duration of PsA of 51.5 ± 13.8 and 5.5 ± 8.4 years were recruited. Indian was overrepresented compared with the national distribution of ethnicities. Compared to Chinese, Indian patients were more likely to be using biological therapies, have higher tender joint count, and worse enthesitis. Higher proportion of Indians had higher disease activity categories measured by cDAPSA, CPDAI, and MDA and had poorer physical function. In the multivariable analysis, ethnicity was significantly associated with HAQ and SF36-PF. Compared to Chinese, Indians with PsA living in the same environment had worse disease activity and physical function measured by validated outcomes.