On the dual contrast enhancement mechanism in frequency-selective inversion-recovery magnetic resonance angiography (IRON-MRA)

The susceptibility of blood changes after administration of a paramagnetic contrast agent that shortens T(1). Concomitantly, the resonance frequency of the blood vessels shifts in a geometry-dependent way. This frequency change may be exploited for incremental contrast generation by applying a frequency-selective saturation prepulse prior to the imaging sequence. The dual origin of vascular enhancement depending first on off-resonance and second on T(1) lowering was investigated in vitro, together with the geometry dependence of the signal at 3T. First results obtained in an in vivo rabbit model are presented.

Improved three-dimensional free-breathing coronary magnetic resonance angiography using gadocoletic acid (B-22956) for intravascular contrast enhancement.

PURPOSE: To evaluate gadocoletic acid (B-22956), a gadolinium-based paramagnetic blood pool agent, for contrast-enhanced coronary magnetic resonance angiography (MRA) in a Phase I clinical trial, and to compare the findings with those obtained using a standard noncontrast T2 preparation sequence. MATERIALS AND METHODS: The left coronary system was imaged in 12 healthy volunteers before B-22956 application and 5 (N = 11) and 45 (N = 7) minutes after application of 0.075 mmol/kg of body weight (BW) of B-22956. Additionally, imaging of the right coronary system was performed 23 minutes after B-22956 application (N = 6). A three-dimensional gradient echo sequence with T2 preparation (precontrast) or inversion recovery (IR) pulse (postcontrast) with real-time navigator correction was used. Assessment of the left and right coronary systems was performed qualitatively (a 4-point visual score for image quality) and quantitatively in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel sharpness, visible vessel length, maximal luminal diameter, and the number of visible side branches. RESULTS: Significant (P < 0.01) increases in SNR (+42%) and CNR (+86%) were noted five minutes after B-22956 application, compared to precontrast T2 preparation values. A significant increase in CNR (+40%, P < 0.05) was also noted 45 minutes postcontrast. Vessels (left anterior descending artery (LAD), left coronary circumflex (LCx), and right coronary artery (RCA)) were also significantly (P < 0.05) sharper on postcontrast images. Significant increases in vessel length were noted for the LAD (P < 0.05) and LCx and RCA (both P < 0.01), while significantly more side branches were noted for the LAD and RCA (both P < 0.05) when compared to precontrast T2 preparation values. CONCLUSION: The use of the intravascular contrast agent B-22956 substantially improves both objective and subjective parameters of image quality on high-resolution three-dimensional coronary MRA. The increase in SNR, CNR, and vessel sharpness minimizes current limitations of coronary artery visualization with high-resolution coronary MRA.

Contrast enhanced breast ultrasound to differentiate papillomas from intraductal secretion : initial experience : P22

Purpose: To describe low mechanical index grey scale contrast enhanced breast ultrasound in patients with intraductal echogenic material in the differentiation of papillomas from intraductal secretions. Methods and materials: In five patients with echographically detected ductal dilatation containing echogenic material low mechanical index grey scale contrast enhanced ultrasonography was performed. No patient had nipple discharge. The examination was performed with a 9 MHz linear transducer after injection of 4 ml of Sonovue. It was assessed if contrast enhancement was present or not. The results were correlated with histologic results after surgical resection or percutaneous biopsy when performed. Results: In 3 patients contrast enhancement was observed. These patients were operated and the papillomas confirmed by histology. In two patients no contrast enhancement was observed. In one of these two patients percutaneous biopsy was performed without evidence of a papillary lesion. The second patient presented with multiple dilated ducts containing echogenic material. No biopsy was performed but breast MRI showed no intraductal enhancement supporting the non papillary nature of the intraductal material. Conclusion: This pilot study shows that contrast enhanced ultrasound is able to detect the vascularisation of papillomas and that it may differentiate intraductal papillomas from secretions.

Contrast agent-enhanced, free-breathing, three-dimensional coronary magnetic resonance angiography.

For free-breathing, high-resolution, three-dimensional coronary magnetic resonance angiography (MRA), the use of intravascular contrast agents may be helpful for contrast enhancement between coronary blood and myocardium. In six patients, 0.1 mmol/kg of the intravascular contrast agent MS-325/AngioMARK was given intravenously followed by double-oblique, free-breathing, three-dimensional inversion-recovery coronary MRA with real-time navigator gating and motion correction. Contrast-enhanced, three-dimensional coronary MRA images were compared with images obtained with a T2 prepulse (T2Prep) without exogenous contrast. The contrast-enhanced images demonstrated a 69% improvement in the contrast-to-noise ratio (6.6 +/- 1.1 vs. 11.1 +/- 2.5; P < 0.01) compared with the T2Prep approach. By using the intravascular agent, extensive portions (> 80 mm) of the native left and right coronary system could be displayed consistently with sub-millimeter in-plane resolution. The intravascular contrast agent, MS-325/AngioMARK, leads to a considerable enhancement of the blood/muscle contrast for coronary MRA compared with T2Prep techniques. The clinical value of the agent remains to be defined in a larger patient series. J. Magn. Reson. Imaging 1999;10:790-799.

Positive contrast MR-lymphography using inversion recovery with ON-resonant water suppression (IRON).

PURPOSE: To investigate the utility of inversion recovery with ON-resonant water suppression (IRON) to create positive signal in normal lymph nodes after injection of superparamagnetic nanoparticles. MATERIALS AND METHODS: Experiments were conducted on six rabbits, which received a single bolus injection of 80 mumol Fe/kg monocrystalline iron oxide nanoparticle (MION-47). Magnetic resonance imaging (MRI) was performed at baseline, 1 day, and 3 days after MION-47 injection using conventional T(1)- and T(2)*-weighted sequences and IRON. Contrast-to-noise ratios (CNR) were measured in blood and in paraaortic lymph nodes. RESULTS: On T(2)*-weighted images, as expected, signal attenuation was observed in areas of paraaortic lymph nodes after MION-47 injection. However, using IRON the paraaortic lymph nodes exhibited very high contrast enhancement, which remained 3 days after injection. CNR with IRON was 2.2 +/- 0.8 at baseline, increased markedly 1 day after injection (23.5 +/- 5.4, P < 0.01 vs. baseline), and remained high after 3 days (21.8 +/- 5.7, *P < 0.01 vs. baseline). CNR was also high in blood 1 day after injection (42.7 +/- 7.2 vs. 1.8 +/- 0.7 at baseline, P < 0.01) but approached baseline after 3 days (1.9 +/- 1.4, P = NS vs. baseline). CONCLUSION: IRON in conjunction with superparamagnetic nanoparticles can be used to perform 'positive contrast' MR-lymphography, particularly 3 days after injection of the contrast agent, when signal is no longer visible within blood vessels. The proposed method may have potential as an adjunct for nodal staging in cancer screening.

Performance of a new gadolinium-based intravascular contrast agent in free-breathing inversion-recovery 3D coronary MRA.

In three-dimensional (3D) coronary magnetic resonance angiography (MRA), the in-flow contrast between the coronary blood and the surrounding myocardium is attenuated as compared to thin-slab two-dimensional (2D) techniques. The application of a gadolinium (Gd)-based intravascular contrast agent may provide an additional source of signal and contrast by reducing T(1blood) and supporting the visualization of more distal or branching segments of the coronary arterial tree. In six healthy adults, the left coronary artery (LCA) system was imaged pre- and postcontrast with a 0.075-mmol/kg bodyweight dose of the intravascular contrast agent B-22956. For imaging, an optimized free-breathing, navigator-gated and -corrected 3D inversion recovery (IR) sequence was used. For comparison, state-of-the-art baseline 3D coronary MRA with T(2) preparation for non-exogenous contrast enhancement was acquired. The combination of IR 3D coronary MRA, sophisticated navigator technology, and B-22956 allowed for an extensive visualization of the LCA system. Postcontrast, a significant increase in both the signal-to-noise ratio (SNR; 46%, P < 0.05) and contrast-to-noise ratio (CNR; 160%, P < 0.01) was observed, while vessel sharpness of the left anterior descending (LAD) artery and the left coronary circumflex (LCX) were improved by 20% (P < 0.05) and 18% (P < 0.05), respectively.

Alveolar echinococcosis of the liver: Diffusion-weighted MRI findings and potential role in lesion characterisation

PURPOSE: To report the diffusion-weighted MRI findings in alveolar echinococcosis (AE) of the liver and evaluate the potential role of apparent diffusion coefficients (ADCs) in the characterisation of lesions. MATERIALS AND METHODS: We retrospectively included 22 patients with 63 AE liver lesions (≥1cm), examined with 3-T liver MRI, including a free-breathing diffusion-weighted single-shot echo-planar imaging sequence (b-values=50, 300 and 600s/mm(2)). Two radiologists jointly assessed the following lesion features: size, location, presence of cystic and/or solid components (according to Kodama's classification system), relative contrast enhancement, and calcifications (on CT). The ADCtotal, ADCmin and ADCmax were measured in each lesion and the surrounding liver parenchyma. RESULTS: Three type 1, 19 type 2, 17 type 3, three type 4 and 21 type 5 lesions were identified. The mean (±SD) ADCtotal, ADCmin and ADCmax for all lesions were 1.73±0.50, 0.76±0.38 and 2.63±0.76×10(-3)mm(2)/s, respectively. The mean ADCtotal for type 1, type 2, type 3, type 4 and type 5 lesions were 1.97±1.01, 1.76±0.53, 1.73±0.41, 1.15±0.42 and 1.76±0.44×10(-3)mm(2)/s, respectively. No significant differences were found between the five lesion types, except for type 4 (p=0.0363). There was a significant correlation between the presence of a solid component and low ADCmin (r=0.39, p=0.0016), whereas an inverse correlation was found between the relative contrast enhancement and ADCtotal (r=-0.34, p=0.0072). CONCLUSION: The ADCs of AE lesions are relatively low compared to other cystic liver lesions, which may help in the differential diagnosis. Although ADCs are of little use to distinguish between the five lesion types, their low value reflects the underlying solid component.

Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group.

Currently, the most widely used criteria for assessing response to therapy in high-grade gliomas are based on two-dimensional tumor measurements on computed tomography (CT) or magnetic resonance imaging (MRI), in conjunction with clinical assessment and corticosteroid dose (the Macdonald Criteria). It is increasingly apparent that there are significant limitations to these criteria, which only address the contrast-enhancing component of the tumor. For example, chemoradiotherapy for newly diagnosed glioblastomas results in transient increase in tumor enhancement (pseudoprogression) in 20% to 30% of patients, which is difficult to differentiate from true tumor progression. Antiangiogenic agents produce high radiographic response rates, as defined by a rapid decrease in contrast enhancement on CT/MRI that occurs within days of initiation of treatment and that is partly a result of reduced vascular permeability to contrast agents rather than a true antitumor effect. In addition, a subset of patients treated with antiangiogenic agents develop tumor recurrence characterized by an increase in the nonenhancing component depicted on T2-weighted/fluid-attenuated inversion recovery sequences. The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies. The Response Assessment in Neuro-Oncology Working Group is an international effort to develop new standardized response criteria for clinical trials in brain tumors. In this proposal, we present the recommendations for updated response criteria for high-grade gliomas.

Navigator-gated free-breathing three-dimensional balanced fast field echo (TrueFISP) coronary magnetic resonance angiography.

RATIONALE AND OBJECTIVES: Recent developments of MR imaging equipment enabled high-quality steady state-free-precession (Balanced FFE, True-FISP) MR-imaging with a substantial 'T2 like' contrast, resulting in a high signal intensity of the blood-pool without the application of exogenous contrast agents. It is hypothesized that Balanced-FFE may be valuable for contrast enhancement in 3D free-breathing coronary MRA. MATERIALS AND METHODS: Navigator-gated free-breathing cardiac triggered coronary MRA was performed in 10 healthy adult subjects and three patients with radiograph defined coronary artery disease using a segmented k-space 3D Balanced FFE imaging sequence. RESULTS: High contrast-to-noise ratio between the blood-pool and the myocardium (29 +/- 8) and long segment visualization of both coronary arteries could be obtained in about 5 minutes during free breathing using the present navigator-gated Balanced-FFE coronary MRA approach. First patient results demonstrated successful display of coronary artery stenoses. CONCLUSION: Balanced FFE offers a potential alternative for endogenous contrast enhancement in navigator-gated free-breathing 3D coronary MRA. The obtained results together with the relatively short scanning time warrant further studies in larger patient collectives.

Targeting Angiogenesis in Glioma - Challenges and Pitfalls

Malignant gliomas, notably glioblastoma are among the most vascularized and angiogenic cancers, and microvascular proliferation is one of the hallmarks for the diagnosis of glioblastoma. Angiogenesis is regulated by a balance of pro- and antiangiogenic signals; overexpression of VEGF and activation of its receptors, most notable VEGFR-2 and -3, results in endothelial cell proliferation and leaky vasculature. Heterogeneous perfusion and oxygenation, peritumoral edema and increased interstitial pressure are the consequence. Both endothelial and tumour cells are strongly dependent on integrin-mediated adhesion for cell proliferation, survival, migration and invasion.Strategies aiming at inhibition of cell signaling and angiogenesis, including integrin inhibitors, have been clinically investigated in gliomas over the last 5 years. Radiological responses, a decreased requirement of corticosteroids and temporary improvement in performance status have repeatedly been observed. Toxicity was mild-moderate and manageable, notably there was no evidence for a substantially increased incidence of intracranial bleeding. However definitive comparative (randomized !) investigation has failed to demonstrate improved outcome with singleagent inhibition of EGFR, or PDGFR or VEGF/VEGFRs pathways in recurrent glioblastoma. Definitive phase III trials combining the anti- VEGF monoclonal antibody bevacizumab, or cilengitide, a peptidic integrininhibitor, together with temozolomide and radiotherapy are ongoing (accrual completed).The integration of anti-angiogenic strategies in the management of malignant glioma also poses entirely new challenges in patient management: 1) Many agents are known for increasing the risk of thrombosis, embolism and intracranial bleeding. 2) Evaluation of treatment efficacy is difficult and new biomarkers of activity, including functional, metabolic or molecular imaging techniques are urgently needed. Normalization of vasculature leads to decrease in contrast enhancement without necessarily reflecting tumour shrinkage. Tumour heterogeneity, putative prognostic or predictive factors require early controlled trials, novel trial designs and endpoints.3) Activation of alternate pathways and tumour escape mechanisms may require combination of multiple agents, which is often not feasible due to regulatory restrictions and potential complex toxicities. Emerging clinical and experimental evidence suggests that anti-angiogenic drugs might need to be combined with drugs targeting tumour adaptive mechanisms in addition to cytotoxic chemotherapy and irradiation for a maximal antitumour effect.

Alveolar echinococcosis of the liver: diffusionweighted MR imaging findings

Purpose: To report the diffusion-weighted MR imaging (DWI) findings in hepatic alveolar echinococcosis (AE). To evaluate the usefulness of apparent diffusion coefficients (ADCs) for differentiating the 5 types of AE lesions (as reported by Kodama, Radiology, 2003).Methods and Materials: We retrospectively included 17 patients (10 women, mean age 64.3years) with 48 AE liver lesions (>1cm2) that had been investigated by 3-Tesla MR imaging between March 2008 and August 2011 performing our standard protocol including DWI (b-values: 0, 300 and 600s/mm2). In consensus, two radiologists assessed lesion characteristics such as diameter, cystic and/or fibrotic components including Kodama classification, signal intensity, contrast enhancement, calcifications (on CT), and measured the ADC of each lesion. AE was confirmed by serology, biopsy and/or surgery in all patients.Results: Seventeen lesions of Kodama type 1, 10 of type 2, 19 of type 3, 1 of type 4 and 1 of type 5 were found. Mean(±SD) ADC of all AE lesions was 1.75±0.45 ×10-3mm2/s. Mean(±SD) ADCs of Kodama type 1, 2, 3, 4 and 5 lesions were 1.74±0.55, 1.71±0.49, 1.82±0.36, 1.46±0 and 1.43±0 ×10-3mm2/s, respectively. No significant difference was noted between the different Kodama types (p=0.89). Presence of fibrotic (p=0.24) and/or calcified (p=0.90) components, or contrast enhancement (p=0.84) of AE lesions were not correlated with significant differences in ADCs.Conclusion: ADCs of AE lesions are relatively low compared to other cystic liver lesions, which is helpful in suggesting the diagnosis. However, ADCs were not found to be useful for differentiating Kodama types of AE lesions.

Using 80 kVp versus 120 kVp in perfusion CT measurement of regional cerebral blood flow.

Perfusion CT studies of regional cerebral blood flow (rCBF), involving sequential acquisition of cerebral CT sections during IV contrast material administration, have classically been reported to be achieved at 120 kVp. We hypothesized that using 80 kVp should result in the same image quality while significantly lowering the patient's radiation dose, and we evaluated this assumption. In five patients undergoing cerebral CT survey, one section level was imaged at 120 kVp and 80 kVp, before and after IV administration of iodinated contrast material. These four cerebral CT sections obtained in each patient were analyzed with special interest to contrast, noise, and radiation dose. Contrast enhancement at 80 kVp is significantly increased (P < .001), as well as contrast between gray matter and white matter after contrast enhancement (P < .001). Mean noise at 80 kVp is not statistically different (P = .042). Finally, performance of perfusion CT studies at 80 kVp, keeping mAs constant, lowers the radiation dose by a factor of 2.8. We, thus, conclude that 80 kVp acquisition of perfusion CT studies of rCBF will result in increased contrast enhancement and should improve rCBF analysis, with a reduced patient's irradiation.

Breathhold three-dimensional coronary magnetic resonance angiography using real-time navigator technology.

The acquisition duration of most three-dimensional (3D) coronary magnetic resonance angiography (MRA) techniques is considerably prolonged, thereby precluding breathholding as a mechanism to suppress respiratory motion artifacts. Splitting the acquired 3D volume into multiple subvolumes or slabs serves to shorten individual breathhold duration. Still, problems associated with misregistration due to inconsistent depths of expiration and diaphragmatic drift during sustained respiration remain to be resolved. We propose the combination of an ultrafast 3D coronary MRA imaging sequence with prospective real-time navigator technology, which allows correction of the measured volume position. 3D volume splitting using prospective real-time navigator technology, was successfully applied for 3D coronary MRA in five healthy individuals. An ultrafast 3D interleaved hybrid gradient-echoplanar imaging sequence, including T2Prep for contrast enhancement, was used with the navigator localized at the basal anterior wall of the left ventricle. A 9-cm-thick volume, with in-plane spatial resolution of 1.1 x 2.2 mm, was acquired during five breathholds of 15-sec duration each. Consistently, no evidence of misregistration was observed in the images. Extensive contiguous segments of the left anterior descending coronary artery (48 +/- 18 mm) and the right coronary artery (75 +/- 5 mm) could be visualized. This technique has the potential for screening for anomalous coronary arteries, making it well suited as part of a larger clinical MR examination. In addition, this technique may also be applied as a scout scan, which allows an accurate definition of imaging planes for subsequent high-resolution coronary MRA.

Perfusion and diffusion MRI of glioblastoma progression in a four-year prospective temozolomide clinical trial.

PURPOSE: This study was performed to determine the impact of perfusion and diffusion magnetic resonance imaging (MRI) sequences on patients during treatment of newly diagnosed glioblastoma. Special emphasis has been given to these imaging technologies as tools to potentially anticipate disease progression, as progression-free survival is frequently used as a surrogate endpoint. METHODS AND MATERIALS: Forty-one patients from a phase II temolozomide clinical trial were included. During follow-up, images were integrated 21 to 28 days after radiochemotherapy and every 2 months thereafter. Assessment of scans included measurement of size of lesion on T1 contrast-enhanced, T2, diffusion, and perfusion images, as well as mass effect. Classical criteria on tumor size variation and clinical parameters were used to set disease progression date. RESULTS: A total of 311 MRI examinations were reviewed. At disease progression (32 patients), a multivariate Cox regression determined 2 significant survival parameters: T1 largest diameter (p < 0.02) and T2 size variation (p < 0.05), whereas perfusion and diffusion were not significant. CONCLUSION: Perfusion and diffusion techniques cannot be used to anticipate tumor progression. Decision making at disease progression is critical, and classical T1 and T2 imaging remain the gold standard. Specifically, a T1 contrast enhancement over 3 cm in largest diameter together with an increased T2 hypersignal is a marker of inferior prognosis.