The extent and severity of vascular leakage as evidence of tumor aggressiveness in high-grade gliomas

Magnetic resonance imaging reveals heterogeneous regions within high-grade gliomas, such as a contrast-enhanced rim, a necrotic core, and non-contrast-enhanced abnormalities. It is unclear which of these regions best describes tumor aggressiveness. We hypothesized that the vascular leakage volume, reflecting disorganized angiogenesis typical of glioblastoma, would be a strong predictor of clinical outcome. The FLAIR tumor volume, post-gadolinium T1 tumor volume, tumor vascular leakage volume determined by dynamic contrast-enhanced imaging, and volume of the contrast-enhanced rim seen on post-gadolinium T1-weighted images were defined for 20 patients about to undergo treatment for newly diagnosed high-grade gliomas. The potential for imaging characteristics to improve prediction of survival and time to progression over clinical variables was tested by using Cox regression analysis. Single-variable Cox regression analysis of each of the four tumor subvolumes revealed that the vascular leakage volume was the only significant predictor of survival. When the joint effect of clinical variables and the vascular leakage volume were tested for prediction of survival, only the age and the vascular leakage volume were selected as significant predictors. However, when time to progression was tested as a dependent variable, both the vascular leakage volume and the vascular permeability were selected as copredictors, along with surgical status. Our findings suggest that for patients with high-grade glioma, time to progression after radiation therapy is influenced by both underlying biological aggressiveness (vascularity) and volume of aggressive tumor. In contrast, survival depends chiefly on the volume of aggressive tumor at the time of presentation.     

MR evaluation of liver iron overload

Children and young adults with hemolytic anemias requiring frequent transfusions develop increased liver iron content. We evaluated 15 chronically transfused children with sickle cell disease to determine whether spin-echo magnetic resonance (MR) imaging was useful in assessing the degree of iron overload. Quantitative MR parameters were correlated with liver biopsy iron determinations and serum ferritin levels. The best predictor of liver iron was the ratio of the intensities between the liver and paraspinal musculature on somewhat T1 weighted sequence (repetition time 0.5 s, echo time 28 ms), R2 = 0.58. Magnetic resonance was able to separate those patients with liver iron levels greater than 100 micrograms/mg (intensity ratios approximately 0.4), from those with levels less than 100 micrograms/mg (intensity ratios near 1). However, MR was unable to quantitate liver iron in patients with values ranging from 100 to 400 micrograms/mg since similar intensity ratios were present in this range. Thus, MR provides a qualitative rather than quantitative assessment of liver iron overload.     

Doppler US gating of cardiac MR imaging

RATIONALE AND OBJECTIVES: Electrocardiographic (ECG) gating of cardiac magnetic resonance (MR) imaging has been problematic for many reasons. The purpose of this study was to demonstrate the feasibility of using Doppler ultrasound (US) gating, either directly off the moving cardiac wall or the systolic upstroke of the arterial signal from the great vessels in neck, in alternative gating modes. MATERIALS AND METHODS: A 2.5-MHz, range-gated Doppler US device was used with A-mode guidance for gating directly off left ventricular wall motion. A 4- or 8.1-MHz, continuous-wave (CW) Doppler US device was used for gating off the systolic upstroke from the great vessels in the neck. The subject undergoing imaging held the transducer against his chest for range-gated Doppler US and against his neck for 8.1-MHz CW Doppler US. The 4-MHz transducer was strapped to the subject's neck. Modified Doppler signals were fed back into the gating circuitry of the MR imager to achieve cardiac synchrony. RESULTS: Cardiac gating was achieved by using both the range-gated technique directly off the cardiac wall and the CW method off blood flow from the great vessels. Problems occurred with radiofrequency shielding during the range-gated method; however, these problems were almost completely removed by use of the CW Doppler probes. CONCLUSION: Doppler US gating of MR images is possible and potentially could overcome many shortcomings of ECG gating. Subsequent embodiments of the technique will require improved radiofrequency shielding in the range-gated technique.     

大剂量甘露醇治疗癌性颅内高压症1例

1 临床资料患者、女性、38岁、因右小细胞肺癌术后16 mo,间断性头痛10 mo,加重1 wk后于2003-01-01入院.在2002-02因枕部疼痛,行头颅CT示: 脑多发转移癌.行多次头颅局部X-刀、γ-刀加全脑预防性放疗和化疗,疗效达部分缓解.2002-12末头痛症状复发,约1.5 h发作1次,伴短暂意识丧失、喷射状呕吐和四肢抽搐.     

DCE and DW-MRI monitoring of vascular disruption following VEGF-Trap treatment of a rat glioma model

Vascular‐targeted therapies have shown promise as adjuvant cancer treatment. As these agents undergo clinical evaluation, sensitive imaging biomarkers are needed to assess drug target interaction and treatment response. In this study, dynamic contrast enhanced MRI (DCE‐MRI) and diffusion‐weighted MRI (DW‐MRI) were evaluated for detecting response of intracerebral 9 L gliosarcomas to the antivascular agent VEGF‐Trap, a fusion protein designed to bind all forms of Vascular Endothelial Growth Factor‐A (VEGF‐A) and Placental Growth Factor (PGF). Rats with 9 L tumors were treated twice weekly for two weeks with vehicle or VEGF‐Trap. DCE‐ and DW‐MRI were performed one day prior to treatment initiation and one day following each administered dose. Kinetic parameters (K^trans, volume transfer constant; k_ep, efflux rate constant from extravascular/extracellular space to plasma; and v_p, blood plasma volume fraction) and the apparent diffusion coefficient (ADC) over the tumor volumes were compared between groups. A significant decrease in kinetic parameters was observed 24 hours following the first dose of VEGF‐Trap in treated versus control animals (p < 0.05) and was accompanied by a decline in ADC values. In addition to the significant hemodynamic effect, VEGF‐Trap treated animals exhibited significantly longer tumor doubling times (p < 0.05) compared to the controls. Histological findings were found to support imaging response metrics. In conclusion, kinetic MRI parameters and change in ADC have been found to serve as sensitive and early biomarkers of VEGF‐Trap anti‐vascular targeted therapy. Copyright © 2011 John Wiley & Sons, Ltd.     

Signal quality of single dose gadobenate dimeglumine pulmonary MRA examinations exceeds quality of MRA performed with double dose gadopentetate dimeglumine

During a recent multi-center trial assessing gadolinium (Gd)-enhanced magnetic resonance angiography (MRA) for diagnosis of acute pulmonary embolism (PE), the Food and Drug Administration announced a risk of nephrogenic sclerosing fibrosis in patients with renal insufficiency who had received intravenous Gd-based MR contrast agents. Although no patients in this trial had renal insufficiency, in cautious response to this announcement, the trial protocol was changed from an intravenous administration of 0.2?mmol/Kg of a conventional Gd-based MR contrast agent to 0.1?mmol/Kg of gadobenate dimeglumine. The study described herein compares the signal quality of pulmonary MRA performed with double dose conventional agent to single dose gadobenate dimeglumine. This study is a retrospective analysis of data from a prospective, multicenter study in men and women ??18?years with documented presence or absence of PE. The study was approved by the Institutional Review Board at all participating centers, and all patients provided written indication of informed consent. We performed both objective and subjective analysis of pulmonary artery image quality. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the main pulmonary artery were assessed in single and double dose protocols and compared. SNR and CNR of the main PA were correlated with subjective quality assessment of main/lobar, segmental and subsegmental pulmonary arteries. Although there were individual outliers, both SNR (P?=?0.01) and CNR (P?=?0.008) were higher in all quartiles for examinations using gadobenate dimeglumine than with gadopentetate dimeglumine. Subjective quality of vascular signal intensity at each vessel order was significantly better for gadobenate dimeglumine (P?<?0.0001), and correlated well with SNR and CNR at each order (<0.001). Because of agent high relaxivity, a single dose of gadobenate dimeglumine provides better pulmonary MRA signal quality than double dose of a conventional Gd-based MR contrast agent.