40 research outputs found
Motion correction of free-breathing magnetic resonance renography using model-driven registration
Introduction
Model-driven registration (MDR) is a general approach to remove patient motion in quantitative imaging. In this study, we investigate whether MDR can effectively correct the motion in free-breathing MR renography (MRR).
Materials and methods
MDR was generalised to linear tracer-kinetic models and implemented using 2D or 3D free-form deformations (FFD) with multi-resolution and gradient descent optimization. MDR was evaluated using a kidney-mimicking digital reference object (DRO) and free-breathing patient data acquired at high temporal resolution in multi-slice 2D (5 patients) and 3D acquisitions (8 patients). Registration accuracy was assessed using comparison to ground truth DRO, calculating the Hausdorff distance (HD) between ground truth masks with segmentations and visual evaluation of dynamic images, signal-time courses and parametric maps (all data).
Results
DRO data showed that the bias and precision of parameter maps after MDR are indistinguishable from motion-free data. MDR led to reduction in HD (HDunregistered = 9.98 ± 9.76, HDregistered = 1.63 ± 0.49). Visual inspection showed that MDR effectively removed motion effects in the dynamic data, leading to a clear improvement in anatomical delineation on parametric maps and a reduction in motion-induced oscillations on signal-time courses.
Discussion
MDR provides effective motion correction of MRR in synthetic and patient data. Future work is needed to compare the performance against other more established methods
Functional Annotation of ESR1 Gene Fusions in Estrogen Receptor-Positive Breast Cancer
RNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor-positive (ER+) breast cancer, but their role in disease pathogenesis remains unclear. We examined multiple ESR1 fusions and found that two, both identified in advanced endocrine treatment-resistant disease, encoded stable and functional fusion proteins. In both examples, ESR1-e6>YAP1 and ESR1-e6>PCDH11X, ESR1 exons 1–6 were fused in frame to C-terminal sequences from the partner gene. Functional properties include estrogen-independent growth, constitutive expression of ER target genes, and anti-estrogen resistance. Both fusions activate a metastasis-associated transcriptional program, induce cellular motility, and promote the development of lung metastasis. ESR1-e6>YAP1- and ESR1-e6>PCDH11X-induced growth remained sensitive to a CDK4/6 inhibitor, and a patient-derived xenograft (PDX) naturally expressing the ESR1-e6>YAP1 fusion was also responsive. Transcriptionally active ESR1 fusions therefore trigger both endocrine therapy resistance and metastatic progression, explaining the association with fatal disease progression, although CDK4/6 inhibitor treatment is predicted to be effective. Lei et al. show that transcriptionally active estrogen receptor gene (ESR1) fusions identified from late-stage, treatment-refractory estrogen receptor-positive (ER+) breast cancer drive pan-endocrine therapy resistance and metastatic progression. Growth of breast tumors driven by ESR1 fusions at primary and metastatic sties can be suppressed with a CDK4/6 inhibitor
Corrosion resistance of zeolite coated mild steel in chloride environment
1229-1234Corrosion resistance of as-synthesized ZSM-5 coating on mild steel sheet in 3.5 wt% NaCl solutions was studied by weight loss method as well as electrochemical method. The first method monitored the extent of corrosion as a function of time (up to 9 days), whereas the latter was performed for 3 h. Results revealed the zeolite coating to be offering superior inhibition of corrosion. It provides an alternate choice of material selection to other environmentally harmful coating materials
Activity and toxicity of 2-CDA in Langerhans cell histiocytosis: A single institutional experience
Background : Langerhans cell histiocytosis (LCH) is a rare disorder
characterized by clonal proliferation of immature and abnormal bone
marrow derived langerhans cells. Treatment is usually multimodal.
Potent anti-monocyte as well as immunomodulatory activity of 2-CDA and
its proven efficacy in many lymphoproliferative disorders has made
2-CDA a rational choice in treatment of LCH. Aim : To evaluate the
efficacy and toxicity profile of 2-CDA in children with relapsed or
refractory LCH. Setting and Design : This is a pilot study and we
present the initial data of the first seven patients treated at our
institution. Materials and Methods : Seven patients of relapsed and
refractory LCH were enrolled from July 2000 to June 2004. The cohort of
seven patients included six males and one female with a median age at
initiation of cladribine was 2.25 years (range, 1.67 to 7.0 years).
Three patients had received one prior chemotherapy regimen while the
rest were heavily pretreated. Cladribine was administered over two
hours IV daily for five days and repeated every four weeks. Results :
After a median of six courses of cladribine (range, 2 to 9), two (33%)
patients achieved PR and two (33%) patients have SD on imaging but are
clinically better. None experienced grade 3 or 4 hematologic toxicity.
At a median follow-up of 19 months (range, 8 to 52 months), five
patients remain alive and one patient has died. Conclusion : Our study
shows that single agent 2-CDA is active and well-tolerated in children
with relapsed or refractory LCH
Activity and toxicity of 2-CDA in Langerhans cell histiocytosis: A single institutional experience
Background : Langerhans cell histiocytosis (LCH) is a rare disorder
characterized by clonal proliferation of immature and abnormal bone
marrow derived langerhans cells. Treatment is usually multimodal.
Potent anti-monocyte as well as immunomodulatory activity of 2-CDA and
its proven efficacy in many lymphoproliferative disorders has made
2-CDA a rational choice in treatment of LCH. Aim : To evaluate the
efficacy and toxicity profile of 2-CDA in children with relapsed or
refractory LCH. Setting and Design : This is a pilot study and we
present the initial data of the first seven patients treated at our
institution. Materials and Methods : Seven patients of relapsed and
refractory LCH were enrolled from July 2000 to June 2004. The cohort of
seven patients included six males and one female with a median age at
initiation of cladribine was 2.25 years (range, 1.67 to 7.0 years).
Three patients had received one prior chemotherapy regimen while the
rest were heavily pretreated. Cladribine was administered over two
hours IV daily for five days and repeated every four weeks. Results :
After a median of six courses of cladribine (range, 2 to 9), two (33%)
patients achieved PR and two (33%) patients have SD on imaging but are
clinically better. None experienced grade 3 or 4 hematologic toxicity.
At a median follow-up of 19 months (range, 8 to 52 months), five
patients remain alive and one patient has died. Conclusion : Our study
shows that single agent 2-CDA is active and well-tolerated in children
with relapsed or refractory LCH
Clinico-biologic profile of Langerhans cell histiocytosis: A single institutional study
Context: Langerhans cell histiocytosis (LCH) is a rare atypical
cellular disorder characterized by clonal proliferation of Langerhans
cells leading to myriad clinical presentations and highly variable
outcomes. There is a paucity of Indian studies on this subject. Aim: To
present the experience of management of LCH at a single institution.
Settings and Design: This is a retrospective observational study of
patients with LCH who presented at the Tata Memorial Hospital between
January 1987 and December 2002. Materials and Methods: Fifty-two
patients with LCH were treated in the study period. Due to the long
observation period and variability in diagnostic and therapeutic
protocols, the patients were risk-stratified based on present criteria.
The disease pattern, management approaches and treatment outcomes of
patients were recorded. Statistical Analysis Used: Statistical
analyses were done using Student\u2032s \u2032t\u2032 test, test for
proportion and survival estimates based on the Kaplan-Meier method.
Results: The median age at presentation was 3 years and more than 48%
of the patients had Group I disease. Skeleton, skin and lymphoreticular
system were the commonly involved organs. Majority (80%) required some
form of therapy. The projected overall survival is 63% at 10 years and
mean survival is 118 months. Seventeen percent of surviving patients
developed long-term sequelae. Conclusions: The clinico-biologic
profile of LCH patients in India is largely similar to international
patterns except a higher incidence of lymphoreticular involvement.
Majority of the patients respond favorably to therapy and have a good
outcome, except a subset of Group I patients who warrant enrolment in
clinical trials with innovative therapeutic strategies to improve
outcome