Validation of a hybrid Doppler ultrasound vessel-based registration algorithm for neurosurgery

Purpose

We describe and validate a novel hybrid nonlinear vessel registration algorithm for intra-operative updating of preoperative magnetic resonance (MR) images using Doppler ultrasound (US) images acquired on the dura for the correction of brain-shift and registration inaccuracies. We also introduce an US vessel appearance simulator that generates vessel images similar in appearance to that acquired with US from MR angiography data.

Methods

Our registration uses the minimum amount of preprocessing to extract vessels from the raw volumetric images. This prevents the removal of important registration information and minimizes the introduction of artifacts that may affect robustness, while reducing the amount of extraneous information in the image to be processed, thus improving the convergence speed of the algorithm. We then completed 3 rounds of validation for our vessel registration method for robustness and accuracy using (i) a large number of synthetic trials generated with our US vessel simulator, (ii) US images acquired from a real physical phantom made from polyvinyl alcohol cryogel, and (iii) real clinical data gathered intra-operatively from 3 patients.

Results

Resulting target registration errors (TRE) of less than 2.5?mm are achieved in more than 90?% of the synthetic trials when the initial TREs are less than 20?mm. TREs of less than 2?mm were achieved when the technique was applied to the physical phantom, and TREs of less than 3?mm were achieved on clinical data.

Conclusions

These test trials show that the proposed algorithm is not only accurate but also highly robust to noise and missing vessel segments when working with US images acquired in a wide range of real-world conditions.     

Long-term cryopreservation of autologous stem cell grafts: a clinical and experimental study of hematopoietic and immunocompetent cells

BACKGROUND: Autologous stem cell transplantation (ASCT) is used in the treatment of several malignancies. Harvesting sufficient peripheral blood progenitor cells (PBPCs) for a potential second autotransplantation at the time of relapse several years after diagnosis is becoming an increasingly common practice.
STUDY DESIGN AND METHODS: Cryopreserved PBPCs were prepared with different concentrations of dimethyl sulfoxide (DMSO; 2, 4, 5, and 10%) and stored for at least 5 years before the recovery of CD34+ cells and various T- and natural killer (NK)-cell subsets were analyzed by flow cytometry. Furthermore, clinical variables for myeloma patients having a second autotransplantation with long-term-stored autografts were evaluated.
RESULTS: The number of viable CD34+ cells in long-term-stored grafts was higher when autografts were cryopreserved with 4 or 5% than with 2 and 10% DMSO. The number of viable CD34+ cells was reduced by 13.9% after 5 years of cryostorage in 5% DMSO. Lymphocyte viability was also higher with 4 or 5% DMSO. However, the frequencies of several T-cell subsets showed DMSO-dependent differences, whereas NK-cell subsets did not. Furthermore, after a second autotransplantation with long-term-stored PBPC grafts at the time of myeloma relapse (median storage time, 42 months) all 17 patients reached neutrophil counts exceeding 0.5 × 10⁹/L and platelet counts exceeding 20 × 10⁹/L within 15 days. There was no difference in engraftment between patients receiving autografts preserved with 5 and 10% DMSO.
CONCLUSION: PBPC autografts can safely be stored for at least 5 years in 5% DMSO and used for ASCT.     

Chronic exposure to carbon monoxide and nicotine: endothelin ET(A) receptor antagonism attenuates carbon monoxide-induced myocardial hypertrophy in rat.

The aims of the present study were to determine the effects of endothelin ET(A) receptor antagonism on carbon monoxide (CO)-induced cardiac hypertrophy and endothelin-1 (ET-1) expression and to compare myocardial effects of chronic nicotine with CO exposure. Female Sprague-Dawley rats (n = 84) were randomized to three groups exposed 20 h/day to CO (200 ppm), nicotine (500 microg/m3), or air for 14 consecutive days. In each exposure group, animals were randomized to ET(A) receptor antagonist LU 135252 in drinking water (0.5 mg/ml) or placebo. Myocardial ET-1 and atrial natriuretic peptide (ANP) expression was measured by competitive RT-PCR and plasma ET-1 by immunoassay. Carboxyhemoglobin was 22.1 +/- 0.3% in CO-exposed animals and 2.8 +/- 0.3% in controls. Plasma nicotine was 57 +/- 7 ng/ml and plasma cotinine was 590 +/- 23 ng/ml in nicotine-exposed animals and below detection levels in controls. CO exposure induced a 21% increase in right ventricular hypertrophy (p < 0.01), a 7% increase in left ventricular hypertrophy (p < 0.01), a 25% increase in right ventricular ET-1 expression (p < 0.05), and an eightfold increase in ANP expression (p = 0.08). ET(A) receptor antagonism reduced right ventricular hypertrophy by 60% (p < 0.05) with no significant effect on left ventricular hypertrophy or myocardial ET-1 expression. Chronic nicotine exposure did not significantly affect cardiac weights or ANP and ET-1 expression. We conclude that ET(A) receptor antagonism reduces right ventricular hypertrophy induced by chronic CO exposure, whereas CO-induced myocardial ET-1 expression remains unchanged.     

T cells raised against allogeneic HLA-A2/CD20 kill primary follicular lymphoma and acute lymphoblastic leukemia cells

T cells mediating a graft‐versus‐leukemia/lymphoma effects without causing graft‐versus‐host disease would greatly improve the safety and applicability of hematopoietic stem cell transplantation. We recently demonstrated that highly peptide‐ and HLA‐specific T cells can readily be generated against allogeneic HLA‐A*02:01 in complex with a peptide from the B cell‐restricted protein CD20. Here, we show that such CD20‐specific T cells can easily be induced from naïve precursors in cord blood, demonstrating that they do not represent cross‐reactive memory cells. The cells displayed high avidity and mediated potent cytotoxic effects on cells from patients with the CD20^pos B cell malignancies follicular lymphoma (FL) and acute lymphoblastic leukemia (ALL). However, the cytotoxicity was consistently lower for cells from two of the ALL patients. The ALL cells that were less efficiently killed did not display lower surface expression of CD20 or HLA‐A*02:01, or mutations in the CD20 sequence. Peptide pulsing fully restored the levels of cytotoxicity, indicating that they are indeed susceptible to T cell‐mediated killing. Adoptive transfer of CD20‐specific T cells to an HLA‐A*02:01^pos patient requires an HLA‐A*02:01^neg, but otherwise HLA identical, donor. A search clarified that donors meeting these criteria can be readily identified even for patients with rare haplotypes. The results bear further promise for the clinical utility of CD20‐specific T cells in B cell malignancies.     

A phase I/II study of the MDR modulator Valspodar (PSC 833) combined with daunorubicin and cytarabine in patients with relapsed and primary refractory acute myeloid leukemia

The cyclosporine analog Valspodar (PSC 833, Novartis Pharma) is a strong inhibitor of the mdr1 gene product p-glycoprotein (pgp). A phase I/II study was conducted in order to evaluate if addition of Valspodar to treatment with daunorubicin and cytarabine, given to patients with primary refractory or relapsed acute myeloid leukemia, could increase the complete remission rate.Fifty-three patients were treated in cohorts of three to six patients. Twelve patients reached a complete remission in bone marrow, five of whom also normalized their peripheral blood values. Three patients experienced treatment-related deaths from pneumonia, liver failure and cerebral hemorrhage, respectively. It is concluded that Valspodar 10 mg/kg per 24 h in combination with daunorubicin 45 mg/m(2) for 3 days and cytarabine 1 g/m(2) twice daily for 4 days is tolerable in this heavily pre-treated group of patients. Due to the moderate treatment results, the phase II part of the study was ended prematurely. The modulation of only pgp did not give an obvious improvement of the treatment results in this group of patients.     

Are there predilection sites for intracranial meningioma? A population-based atlas

Neurosurgical Review - Meningioma is the most common benign intracranial tumor and is believed to arise from arachnoid cap cells of arachnoid granulations. We sought to develop a population-based...