Combined PET/MRI: from Status Quo to Status Go. Summary Report of the Fifth International Workshop on PET/MR Imaging; February 15-19, 2016; Tübingen, Germany.

This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tübingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.

High spatial resolution and high contrast visualization of brain arteries and veins: impact of blood pool contrast agent and water-selective excitation imaging at 3T.

PURPOSE: To investigate a blood pool contrast agent and water-selective excitation imaging at 3 T for high spatial and high contrast imaging of brain vessels including the veins. METHODS AND RESULTS: 48 clinical patients (47 ± 18 years old) were included. Based on clinical findings, twenty-four patients received a single dose of standard extracellular Gadoterate-meglumine (Dotarem®) and 24 received the blood pool contrast agent Gadofosveset (Vasovist®). After finishing routine MR protocols, all patients were investigated with two high spatial resolution (0.15 mm (3) voxel size) gradient echo sequences in random order in the equilibrium phase (steady-state) as approved by the review board: A standard RF-spoiled gradient-echo sequence (HR-SS, TR/TE 5.1/2.3 msec, FA 30°) and a fat-suppressed gradient-echo sequence with water-selective excitation (HR-FS, 1331 binominal-pulse, TR/TE 8.8/3.8 msec, FA 30°). The images were subjectively assessed (image quality with vessel contrast, artifacts, depiction of lesions) by two investigators and contrast-to-noise ratios (CNR) were compared using the Student's t-test. The image quality and CNR in the HR-FS were significantly superior compared to the HR-SS for both contrast agents (p < 0.05). The CNR was also improved when using the blood pool agent but only to a minor extent while the subjective image quality was similar for both contrast agents. CONCLUSION: The utilized sequence with water-selective excitation improved image quality and CNR properties in high spatial resolution imaging of brain arteries and veins. The used blood pool contrast agent improved the CNR only to a minor extent over the extracellular contrast agent.

[MR imaging of lymph nodes using Gadofluorine M: feasibility in a swine model at 1.5 and 3T]. / MR-Bildgebung von Lymphknoten mit Gadofluorine M in einem Schweinemodell bei 1,5 and 3T.

PURPOSE: To investigate the potential of Gadofluorine M for targeted lymph node imaging in a human size animal model and on a clinical MR scanner at 1.5 and 3 T. MATERIALS AND METHODS: Pelvic and cervical lymph nodes in a swine model were investigated prior to and 24 hours after intravenous administration of 50 micromol/kg body weight Gadofluorine M, an experimental contrast agent. MR imaging was carried out on clinical 1.5 T and 3 T whole-body MR systems using clinically available coils and T 1-weighted sequences. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) with respect to the surrounding tissue were assessed and compared using the Student's t-test. The Gd concentration in the lymph nodes (n = 43) was measured post mortem by Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES). RESULTS: Gadofluorine M allowed for high signal and high contrast visualization of lymph nodes in all stations on post-contrast images with a significantly increased SNR and CNR (SNR pelvic lymph nodes post vs. pre: 46 +/- 7 vs.14 +/- 3, SNR cervical lymph nodes post vs. pre: 105 +/- 64 vs. 32 +/- 21; CNR pelvic lymph node vs. muscle post vs. pre 28 +/- 5 vs. 0.2 +/- 0.5, CNR cervical lymph node vs. muscle post vs. pre 76 +/- 53 vs. 11 +/- 15, p < 0.05 for all comparisons). The SNR and CNR in the pelvis were further improved using 3 T compared to 1.5 T scanners (SNR lymph nodes 3 T vs. 1.5 T 84 +/- 6 vs. 46 +/- 7, CNR lymph node vs. muscle 3 T vs. 1.5 T 53 +/- 9 vs. 28 +/- 5 respectively, p < 0.05). A high concentration of Gd in the lymph nodes was found (149 +/- 25 mmol Gd/L). CONCLUSION: Gadofluorine M accumulates in the lymph nodes and allows for selective targeted high contrast MR imaging of lymph node tissue in a large animal model using clinically available MR imaging techniques. 3 T further improves SNR and CNR compared to 1.5 T.

Molecular coronary MR imaging of human thrombi using EP-2104R, a fibrin-targeted contrast agent: experimental study in a swine model.

PURPOSE: The aim of this study was to investigate the use of a fibrin-specific contrast agent (EP-2104R, EPIX Pharmaceuticals, Lexington, Massachusetts, USA) for targeted molecular magnetic resonance (MR) imaging of human clot material removed from patients in a model of coronary thrombosis in swine. MATERIALS AND METHODS: Freshly ex vivo engineered clots from human blood and human in situ developed clots removed from patients were delivered into the coronary arteries of nine domestic swine. For MR imaging a navigator-gated, free-breathing, cardiac-triggered 3D inversion recovery black-blood gradient echo sequence was performed prior to clot delivery (baseline), after clot delivery but prior to contrast media administration, and two hours after systemic (i.v.) injection of 4 micromol/kg EP-2104R. MR images were analyzed by two investigators and the contrast-to-noise ratio and Gadolinium (Gd) concentration in the clots were assessed. RESULTS: On baseline images and prior to contrast media application no thrombi were visible. Post contrast administration all 10 coronary emboli (five ex vivo engineered clots and five human clots removed from patients) were selectively visualized as white spots with a mean contrast-to-noise ratio to the blood pool and the surrounding tissue of >12 and a mean Gd concentration of >100 microM. CONCLUSION: Molecular MR imaging using the fibrin-targeted contrast agent EP-2104R allows selective visualization of human clot material in a model of coronary thrombosis in swine.

Temperature quantification using the proton frequency shift technique: In vitro and in vivo validation in an open 0.5 tesla interventional MR scanner during RF ablation.

Open magnetic resonance (MR) scanners allow MR-guided targeting of tumors, as well as temperature monitoring of radio frequency (RF) ablation. The proton frequency shift (PFS) technique, an accurate and fast imaging method for temperature quantification, was used to synthesize thermal maps after RF ablation in an open 0.5 T MR system under ex vivo and in vivo conditions. Calibration experiments with 1.5% agarose gel yielded a chemical shift factor of 0.011 +/- 0.001 ppm/ degrees C (r2 = 0.96). Three gradient echo (GRE) pulse sequences were tested for thermal mapping by comparison with fiberoptic thermometer (Luxtron Model 760) readings. Temperature uncertainty decreased from high to low bandwidths (BW): +/-5.9 degrees C at BW = 15.6 kHz, +/-1.4 degrees C at BW = 3.9 kHz, and +/-0.8 degrees C at BW = 2.5 kHz. In vitro experiments (N = 9) in the paraspinal muscle yielded a chemical shift factor of 0.008 +/- 0.001 ppm/ degrees C. Temperature uncertainty was determined as +/-2.7 degrees C (BW = 3.9 kHz, TE = 19.3 msec). The same experiments carried out in the paraspinal muscle (N = 9) of a fully anesthetized pig resulted in a temperature uncertainty of +/-4.3 degrees C (BW = 3.9 kHz, TE = 19.3 msec), which is higher than it is in vitro conditions (P < 0.15). Quantitative temperature monitoring of RF ablation is feasible in a 0.5 T open-configured MR scanner under ex vivo and in vivo conditions using the PFS technique.

Coronary magnetic resonance angiography.

Despite advances in both prevention and treatment, cardiovascular disease remains the leading cause of morbidity and mortality in the United States. The current gold standard for the diagnosis of coronary artery disease is the x-ray coronary angiogram, which is both costly and associated with a small risk of morbidity. More than 1 million Americans are referred for this test annually, and despite the availability of numerous noninvasive tests to identify patients with coronary artery disease, > or =35% of patients referred for this test are found not to have disease. It therefore would be beneficial to use a noninvasive test to allow the presence of coronary atherosclerosis to be determined directly. Coronary magnetic resonance angiography, a technique that is aimed at establishing a noninvasive test for the assessment of significant coronary stenoses, obviates the risks of patient exposure to radiation of x-ray angiography and therefore represents a major step forward in diagnostic cardiology.

Magnetic resonance coronary lumen and vessel wall imaging.

Coronary magnetic resonance angiography (MRA) is a technique aimed at establishing a noninvasive test for the assessment of significant coronary stenoses. There are certain boundary conditions that have hampered the clinical success of coronary MRA and coronary vessel wall imaging. Recent advances in hardware and software allow for consistent visualization of the proximal and mid portions of the native coronary arteries. Current research focuses on the use of intravascular MR contrast agents and black blood coronary angiography. One common goal is to create a noninvasive test which might allow for screening for major proximal and mid coronary artery disease. These novel approaches will represent a major step forward in diagnostic cardiology.

Prosthetic heart valve evaluation by magnetic resonance imaging.

OBJECTIVE: To evaluate the potential of magnetic resonance imaging (MRI) for evaluation of velocity fields downstream of prosthetic aortic valves. Furthermore, to provide comparative data from bileaflet aortic valve prostheses in vitro and in patients. METHODS: A pulsatile flow loop was set up in a 7.0 Tesla MRI scanner to study fluid velocity data downstream of a 25 mm aortic bileaflet heart valve prosthesis. Three dimensional surface plots of velocity fields were displayed. In six NYHA class I patients blood velocity profiles were studied downstream of their St. Jude Medical aortic valves using a 1.5 Tesla MRI whole-body scanner. Blood velocity data were displayed as mentioned above. RESULTS: Fluid velocity profiles obtained from in vitro studies 0.25 valve diameter downstream of the valve exhibited significant details about the cross sectional distribution of fluid velocities. This distribution completely reflected the valve design. Blood velocity profiles in humans were considerably smoother and in some cases skewed with the highest velocities toward the anterior-right ascending aortic wall. CONCLUSION: Display and interpretation of fluid and blood velocity data obtained downstream of prosthetic valves is feasible both in vitro and in vivo using the MRI technique. An in vitro model with a straight tube and the test valve oriented orthogonally to the long axis of the test tube does not entail fluid velocity profiles which are compatible to those obtained from humans, probably due to the much more complex human geometry, and variable alignment of the valve with the ascending aorta. With the steadily improving quality of MRI scanners this technique has significant potential for comparative in vitro and in vivo hemodynamic evaluation of heart valves.

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.

MR guidance of laser disc decompression: preliminary in vivo experience.

The purpose of this study was to perform percutaneous laser disc decompression (PLDD) under MR guidance in an open configuration 0. 5-T MR system. Following failed conservative treatment for 6 months, eight patients with contained disc herniations were enrolled in the study. Following MR guided introduction of the laser fiber into the targeted disc space, the laser-induced temperature distribution was visualized using a color-coded subtraction technique based on a T1-weighted GRE sequence. In seven patients PLDD could be performed. In all cases laser effects were depicted by MR. In this regard the color-coded technique was found to be superior to conventional magnitude images. Whereas no apparent decrease in the extent of herniation was discovered immediately following PLDD, T2-weighted FSE images showed signal intensity alterations in two of the seven patients. Clinical evaluation, obtained 3-4 months after PLDD, revealed a fair (n = 2) or good (n = 4) response to the treatment. One patient showed no change in symptoms. MR guidance and monitoring of PLDD is feasible within an open 0.5-T system and seems to render PLDD more safe and controllable.

Radio-frequency-induced thermoablation: monitoring with T1-weighted and proton-frequency-shift MR imaging in an interventional 0.5-T environment.

PURPOSE: To evaluate the feasibility and accuracy of monitoring radio-frequency (RF) ablation with an open-configuration, 0.5-T magnetic resonance (MR) imager. MATERIALS AND METHODS: Thirty-six in vivo RF ablation experiments were performed in porcine paravertebral muscle (n = 24) and liver (n = 12). A 90 degrees C tip temperature was applied for 3-9 minutes. MR images were acquired after continuous or during intermittent RF application. Temperature changes were monitored as signal intensity and proton-frequency-shift (PFS) alterations in two T1-weighted gradient-echo sequences. An update image was obtained every 2.5 seconds (20/10 [repetition time msec/echo time [TE] msec]) or every 5.0 seconds (40/20). A color-coded subtraction technique enhanced the signal intensity and PFS changes. Macroscopic coagulation size was compared with MR image lesion size. RESULTS: The RF application mode had no significant effect on coagulation size in muscle or liver (P > .05). Twenty-two of 24 coagulative lesions in muscle and nine of 12 in liver were demonstrated with the PFS technique. Accuracy of lesion size determination depended on TE (TE = 20 msec, r = .95; TE = 10 msec, r = .78 [P < .01]). The T1-weighted technique depicted only six of 24 muscle and three of 12 liver lesion ablations. In the lesions depicted, macroscopic size was significantly underestimated (P < .001). CONCLUSION: PFS MR monitoring of RF effects in liver and muscle is feasible and accurate. The PFS technique outperformed the T1-weighted technique.

Monitoring of radio frequency tissue ablation in an interventional magnetic resonance environment. Preliminary ex vivo and in vivo results.

RATIONALE AND OBJECTIVES: The authors evaluate the feasibility of monitoring radio frequency (RF) ablation in an interventional, open-configuration, 0.5-tesla magnetic resonance (MR) environment. METHODS: Ex vivo and in vivo RF coagulation necrosis were induced in porcine paraspinal muscle tissue using a 300 kHz monopolar RF generator applying 5 to 20 W over 3 to 9 minutes. Images were acquired simultaneous to RF application, after RF application, and in an intermittent mode (60 seconds of RF followed by 15 seconds of MR imaging). Temperature changes were monitored based on amplitude (ex vivo) and phase alterations (in vivo) of a T1-weighted graded refocused echo (GRE) sequence enabling an update every 2.5 seconds. A standardized color-coded subtraction technique enhanced signal changes. Additionally, T2- and T1-weighted spin echo (SE) images were acquired with and without intravenous contrast. Macroscopic coagulation size was compared with lesion size seen on MR images. RESULTS: Although lesion diameters were related directly to applied RF power, the application mode had no significant impact on coagulation size (P > 0.05). As could be expected, MR imaging during RF ablation resulted in major image distortion. Radio frequency effects were seen on images acquired in the continuous and intermittent modes. Coagulation size seen on GRE images correlated well with macroscopy both ex vivo (r = 0.89) and in vivo (r = 0.92). Poorer correlation was found with postinterventional SE sequences (r = 0.78-0.84). CONCLUSIONS: Magnetic resonance monitoring of RF effects is feasible both ex vivo as well as in vivo using temperature-sensitive sequences in an open-configuration MR environment.