Imaging alveolar-capillary gas transfer using hyperpolarized 129Xe MRI

Effective pulmonary gas exchange relies on the free diffusion of gases across the thin tissue barrier separating airspace from the capillary red blood cells (RBCs). Pulmonary pathologies, such as inflammation, fibrosis, and edema, which cause an increased blood-gas barrier thickness, impair the efficiency of this exchange. However, definitive assessment of such gas-exchange abnormalities is challenging, because no methods currently exist to directly image the gas transfer process. Here we exploit the solubility and chemical shift of (129)Xe, the magnetic resonance signal of which has been enhanced by 10(5) with hyperpolarization, to differentially image its transfer from the airspaces into the tissue barrier spaces and RBCs in the gas exchange regions of the lung. Based on a simple diffusion model, we estimate that this MR imaging method for measuring (129)Xe alveolar-capillary transfer is sensitive to changes in blood-gas barrier thickness of approximately 5 microm. We validate the successful separation of tissue barrier and RBC images and show the utility of this method in a rat model of pulmonary fibrosis where (129)Xe replenishment of the RBCs is severely impaired in regions of lung injury.     

Postural responses to multidirectional stance perturbations in cerebellar ataxia

Previous studies of patients with focal cerebellar damage underscored the importance of the cerebellum for balance control. These studies were restricted to postural control in the pitch plane, and focused mainly on leg muscle responses. Here, we examined the effect of degenerative cerebellar lesions on postural control in multiple directions, and studied how such lesions affect intersegmental coordination of the legs, trunk and arms. We formulated two main questions. (a) Do patients with cerebellar ataxia predominantly have balance problems in the sagittal or frontal planes? (b) Is instability in cerebellar ataxia associated with increased joint motion or with reduced joint motion? We selected nine patients with autosomal dominant spinocerebellar ataxia (SCA)--three with pure ataxia and six with mild extra-cerebellar features--and 12 matched controls. Upright standing subjects received support surface rotations (7.5 degrees at 60 degrees /s) that were randomly delivered in eight different directions of pitch or roll. We used full body kinematics to determine displacements of the center of mass (COM) and of individual body segments. We also collected surface EMG from 10 leg, trunk and arm muscles. Primary variables of interest were COM displacement and trunk control (angles and muscle responses). Secondary analyses focused on angles and muscle responses of the legs and arms. COM analysis demonstrated that SCA patients had greatest instability following backward and laterally directed perturbations. Major factors in causing this instability were, first, a marked reduction of stimulus-induced knee flexion and, second, excessive "hypermetric" motion of the pelvis (in roll) and trunk (in pitch). Muscle responses of SCA patients were characterized by increased late balance correcting activity. Responses of patients with pure ataxia were comparable to those of patients with mild extra-cerebellar features. A main underlying cause of postural instability in SCA patients appears to be "locking" of the knees, which may reflect compensation (by reducing interaction between body links) or reduced vestibulocerebellar control over leg muscles. The observed pathophysiology is very different from that seen in other patient populations.     

Repetitive transcranial magnetic stimulation to improve mood and motor function in Parkinson's disease

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can produce lasting changes in excitability and activity in cortical regions underneath the stimulation coil (local effect), but also within functionally connected cortical or subcortical regions (remote effects). Since the clinical presentation of Parkinson's disease (PD) is related to abnormal neuronal activity within the basal ganglia and cortical regions, including the primary motor cortex, the premotor cortex and the prefrontal cortex, several studies have used rTMS to improve brain function in PD. Here, we review the studies that have investigated the possible therapeutic effects of rTMS on mood and motor function in PD patients. We highlight some methodological inconsistencies and problems, including the difficulty to define the most effective protocol for rTMS or to establish an appropriate placebo condition. We finally propose future directions of research that may help to improve the therapeutic efficacy of rTMS in PD.     

Breast cancer screening: using familiality for earlier detection

It is the purpose of this study to investigate whether breast cancer in patients with a positive family history is detected at an earlier stage with better prognostic markers than breast cancer in patients without a positive family history. In 481 patients, tumour size, tumour type, lymph vessel invasion, blood vessel invasion, receptor state, lymphatic spread, mitotic activity index (MAI) and survival were measured and compared, according to their family history. No difference was found between patients without a family history, patients with first-degree relatives or patients with second-degree relatives with breast cancer. Tumours were detected in the same stages and prognostic factors, MAI and survival were similar in all groups. A positive family history of breast cancer does not lead to earlier detection of breast cancer or a better survival.     

Popeye proteins: muscle for the aging sinus node

The electrical impulses that dictate the rhythm of the heartbeat in normal situations and during exercise or stress are initiated by a small number of sinus node pacemaker cells. Senescence and dysfunction of the sinus node affects many people later in life, causing physiologically inappropriate heart rates, but the underlying mechanisms are not well understood. In this issue of the JCI, Froese and colleagues show that deficiency in either Popeye domain containing 1 (Popdc1) or Popdc2 leads to sinus node dysfunction under stressed conditions in aged mice. The mechanism reported to underlie the effects of Popdc1/2 deficiency in mice may cause the stress-induced sinus node dysfunction found in many aged individuals and may point to new strategies for therapeutic intervention.     

Comparison of enhancement characteristics between invasive lobular carcinoma and invasive ductal carcinoma

Purpose:

To compare enhancement characteristics between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) on contrast enhanced MRI of the breast and to observe the magnitude of eventual differences as these may impair the diagnostic value of breast MRI in ILC.

Materials and Methods:

We performed an analysis of enhancement characteristics on biphasic breast MRI in a series of 136 patients (103 IDC, 33 ILC) using an in‐house developed application for pharmacokinetic modeling of contrast enhancement and a commercially available CAD application that evaluated the contrast‐enhancement versus time curve.

Results:

Pharmacokinetic analysis showed that the most enhancing voxels in IDC had significantly higher K^trans‐values than in ILC (P < 0.01). No difference in v_e‐values was noted between groups. Visual assessment of contrast‐enhancement versus time curves revealed wash‐out curves to be less common in ILC (48% versus 84%). However, when using the CAD‐application to assess the most malignant looking curve, the difference was blotted out (76% versus 86%).

Conclusion:

ILC enhances slower than IDC but peak enhancement is not significantly less. The use of a CAD‐application may help to determine the most malignant looking contrast‐enhancement versus time curve, and hence facilitates lesion classification. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Comparison of different risk-adjustment models in assessing short-term surgical outcome after transthoracic esophagectomy in patients with esophageal cancer

Background

Different risk-prediction models have been developed, but none is generally accepted in selecting patients for esophagectomy. This study evaluated 5 most frequently used risk-prediction models, including the American Society of Anesthesiologists, Portsmouth-modified Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM), and the adjusted version for Oesophagogastric surgery (O-POSSUM), Charlson and the Age adjusted Charlson score to assess postoperative mortality after transthoracic esophagectomy.

Methods

Data were obtained from 278 consecutive esophageal cancer patients between 1991 and 2007. Performance in predicting postoperative mortality (in-hospital and 90-day mortality) were analyzed regarding calibration (Hosmer and Lemeshow goodness-of-fit test) and discrimination (area under the receiver operator curve).

Results

The Hosmer and Lemeshow goodness-of-fit test was applied to each model and showed a significant outcome for only the P-POSSUM score (P = .035). The receiver operator curve indicated discriminatory power for P-POSSUM (.766) and for O-POSSUM (.756), other models did not exceed the minimal surface of .7.

Conclusions

Postoperative mortality after esophagectomy was best predicted by O-POSSUM. However, it still overpredicted postoperative mortality.     

Survival After Stereotactic Body Radiation Therapy for Clinically Diagnosed or Biopsy-Proven Early-Stage NSCLC: A Systematic Review and Meta-Analysis

Introduction

Stereotactic body radiation therapy (SBRT) is a promising curative treatment for early-stage NSCLC. It is unclear if survival outcomes for SBRT are influenced by a lack of pathological confirmation of malignancy and staging of disease in these patients. In this systematic review and meta-analysis, we assess survival outcomes after SBRT in studies with patients with clinically diagnosed versus biopsy-proven early-stage NSCLC.