GRAPE: a graphical pipeline environment for image analysis in adaptive magnetic resonance imaging

Purpose

We present a platform, GRAphical Pipeline Environment (GRAPE), to facilitate the development of patient-adaptive magnetic resonance imaging (MRI) protocols.

Methods

GRAPE is an open-source project implemented in the Qt C++ framework to enable graphical creation, execution, and debugging of real-time image analysis algorithms integrated with the MRI scanner. The platform provides the tools and infrastructure to design new algorithms, and build and execute an array of image analysis routines, and provides a mechanism to include existing analysis libraries, all within a graphical environment. The application of GRAPE is demonstrated in multiple MRI applications, and the software is described in detail for both the user and the developer.

Results

GRAPE was successfully used to implement and execute three applications in MRI of the brain, performed on a 3.0-T MRI scanner: (i) a multi-parametric pipeline for segmenting the brain tissue and detecting lesions in multiple sclerosis (MS), (ii) patient-specific optimization of the 3D fluid-attenuated inversion recovery MRI scan parameters to enhance the contrast of brain lesions in MS, and (iii) an algebraic image method for combining two MR images for improved lesion contrast.

Conclusions

GRAPE allows graphical development and execution of image analysis algorithms for inline, real-time, and adaptive MRI applications.

     

Epidemiology of treatment-associated mucosal injury after treatment with newer regimens for lymphoma, breast, lung, or colorectal cancer

Goals of work: Oral and gastrointestinal (GI) mucositis are frequent complications of chemotherapy and radiotherapy for cancer, contributing to not only the morbidity of treatment but its cost as well. The risk associated with specific chemotherapeutic agents, alone and in combination, has been characterized previously. In the current study, we sought to estimate the risk associated with newer regimens for the treatment of non-Hodgkin’s lymphoma (NHL) and common solid tumors. Methods: We reviewed published studies reporting phase II and III clinical trials of dose-dense regimens for breast cancer and NHL, TAC (docetaxel, adriamycin, cyclophosphamide) chemotherapy for breast cancer, and infusional 5-fluorouracil-based regimens for colorectal cancer. Platinum-, gemcitabine-, and taxane-based regimens for lung cancer, either alone or in combination with radiotherapy, were also considered. Using modified meta-analysis methods, we calculated quality-adjusted estimates of the risk for oral and GI mucositis by tumor type and regimen. Case reports are used to emphasize the relevance of the findings for patient care. Main results: Our findings demonstrate that mucosal toxicity remains an important complication of cancer treatment. Moreover, innovations in drug combinations, scheduling, or mode of administration significantly modulate the risk for both oral and GI mucositis. Conclusions: Ongoing review of the clinical trial experience will remain important as newer, targeted agents enter standard clinical practice.     

Toward the prevention of acute lung injury: protocol-guided limitation of large tidal volume ventilation and inappropriate transfusion

OBJECTIVE: We evaluated the effect of two quality improvement interventions (low tidal volume ventilation and restrictive transfusion) on the development of acute lung injury in mechanically ventilated patients. DESIGN: Observational cohort study. SETTING: Three intensive care units in a tertiary academic center. PATIENTS: We included patients who were mechanically ventilated for > or =48 hrs excluding those who refused research authorization or had preexisting acute lung injury or pneumonectomy. INTERVENTIONS: Multifaceted interdisciplinary intervention consisting of Web-based teaching, respiratory therapy protocol, and decision support within computerized order entry. MEASUREMENTS AND MAIN RESULTS: Of 375 patients who met the inclusion and exclusion criteria, 212 were ventilated before and 163 after the interventions. Baseline characteristics were similar between the two groups except for a lower frequency of sepsis (27% vs. 17%, p = .030), trend toward lower median glucose level (140 mg/dL, interquartile range 118-168 vs. 132 mg/dL, interquartile range 113-156, p = .096), and lower frequency of pneumonia (27% vs. 20%, p = .130) during the second period. We observed a large decrease in tidal volume (10.6-7.7 mL/kg predicted body weight, p < .001), in peak airway pressure (31-25 cm H2O, p < .001), and in the percentage of transfused patients (63% to 38%, p < .001) after the intervention. The frequency of acute lung injury decreased from 28% to 10% (p < .001). The duration of mechanical ventilation decreased from a median of 5 (interquartile range 4-9) to 4 (interquartile range 4-8) days (p = .030). When adjusted for baseline characteristics in a multivariate logistic regression analysis, protocol intervention was associated with a reduction in the frequency of new acute lung injury (odds ratio 0.21, 95% confidence interval 0.10-0.40). CONCLUSIONS: Interdisciplinary intervention effectively decreased large tidal volumes and unnecessary transfusion in mechanically ventilated patients and was associated with a decreased frequency of new acute lung injury.     

Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients

BACKGROUND: Transfusion has long been identified as a risk factor for acute lung injury (ALI)/ARDS. No study has formally evaluated the transfusion of specific blood products as a risk factor for ALI/ARDS in critically ill medical patients. METHOD: In this single-center retrospective cohort study, 841 consecutive critically ill patients were studied for the development of ALI/ARDS. Patients who received blood product transfusions were compared with those who did not, in univariate and multivariate propensity analyses. RESULTS: Two hundred ninety-eight patients (35%) received blood transfusions. Transfused patients were older (mean [+/- SD] age, 67 +/- 17 years vs 62 +/- 19 years; p < 0.001) and had higher acute physiologic and chronic health evaluation (APACHE) III scores (74 +/- 32 vs 58 +/- 23; p < 0.001) than those who had not received transfusions. ALI/ARDS developed more commonly (25% vs 18%; p = 0.025) in patients exposed to transfusion. Seventeen patients received massive RBC transfusions (ie, > 10 U of blood transfused within 24 h), of whom 13 also received fresh-frozen plasma (FFP) and 11 received platelet transfusions. When adjusted for the probability of transfusion and other ALI/ARDS risk factors, any transfusion was associated with the development of ALI/ARDS (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.24 to 3.75). Among those patients receiving individual blood products, ALI/ARDS was more likely to develop in patients who received FFP transfusions (OR, 2.48; 95% CI, 1.29 to 4.74) and platelet transfusions (OR, 3.89; 95% CI, 1.36 to 11.52) than in those who received only RBC transfusions (OR, 1.39; 95% CI, 0.79 to 2.43). CONCLUSION: Transfusion is associated with an increased risk of the development of ALI/ARDS in critically ill medical patients. The risk is higher with transfusions of plasma-rich blood products, FFP, and platelets, than with RBCs.     

Mesenchymal Stem Cells Display Tumor-Specific Tropism in an RCAS/Ntv-a Glioma Model

Bone marrow-derived mesenchymal stem cells (MSCs) have been shown to localize to gliomas and deliver therapeutic agents. However, the clinical translation of MSCs remains poorly defined because previous studies relied on glioma models with uncertain relevance to human disease, typically xenograft models in immunocompromised mice. To address this shortcoming, we used the RCAS/Ntv-a system, in which endogenous gliomas that recapitulate the tumor and stromal features of human gliomas develop in immunocompetent mice. MSCs were harvested from bonemarrowof Ntv-a mice and injected into the carotid artery of Ntv-a mice previously inoculated with RCAS-PDGF-B and RCAS-IGFBP2 to induce malignant gliomas (n = 9). MSCs were labeled with luciferase for in vivo bioluminescence imaging (BLI). After intra-arterial injection, BLI revealed MSCs in the right frontal lobe in seven of nine mice. At necropsy, gliomas were detected within the right frontal lobe in all these mice, correlating with the location of the MSCs. In the twomice without MSCs based on BLI, no tumor was found, indicating thatMSC localization was tumor specific. In another cohort of mice (n = 9), MSCs were labeled with SP-DiI, a fluorescent vital dye. After intra-arterial injection, fluorescence microscopy revealed SP-DiI-labeled MSCs throughout tumors 1 to 7 days after injection but not in nontumoral areas of the brain. MSCs injected intravenously did not localize to tumors (n = 12). We conclude that syngeneic MSCs are capable of homing to endogenous gliomas in immunocompetent mice. These findings support the use of MSCs as tumor-specific delivery vehicles for treating gliomas.     

Significance of elevated cardiac troponin T levels in critically ill patients with acute respiratory disease

Background

Elevations in cardiac troponin have prognostic importance in critically ill patients. However, there are no data addressing the independent association between troponin levels and mortality, adjusted for the severity of the underlying disease, in patients hospitalized for acute respiratory disorders. We investigated whether troponin T (cTnT) elevations are independently associated with in-hospital mortality in patients in the intensive care unit (ICU) admitted for severe and acute respiratory conditions. After adjusting for the severity of disease measured by the Acute Physiology, Age, and Chronic Health Evaluation (APACHE) III prognostic system, we evaluated short-term (30 days) and long-term (3 years) mortality.

Methods

We studied the APACHE III database and cTnT levels from patients admitted consecutively to the ICU at Mayo Clinic, Rochester, Minnesota. Between January 2001 and December 2005, 2078 patients with respiratory conditions had cTnT measured at ICU admission. In-hospital, short-term (30 days) and long-term (3 years) all-cause mortality were determined.

Results

Of the study patients, 878 (42.3%) had elevated cTnT and 1200 patients (57.7%) had undetectable cTnT. During hospitalization, 1.1% of the patients with troponin T <0.01 ng/mL died compared to 21% of those with troponin T ≥0.01 ng/mL (P <.0001). At 30 days, mortality was 18.6% in patients with elevations of cTnT and 1.5% in patients without elevations of cTnT (P <.0001). The Kaplan-Meier probability of survival at 1-year follow-up was 71.0%, at 2-year follow-up was 48.3%, and 3-year follow-up was 39.4% with troponin T ≥0.01 ng/mL and at 1-year follow-up was 98.8%, at 2-year follow-up was 97.2%, and at 3-year follow-up was 95.5% with troponin T <0.01 μg/L (P <.0001). After adjustment for severity of disease and baseline characteristics, cTnT levels remained associated with in-hospital, short-term and long-term mortality (P <.0001).

Conclusions

In patients admitted to the ICU for respiratory disorders, cTnT elevations are independently associated with in-hospital, short-term and long-term mortality.