Quality Assurance Investigations and Impurity Characterization during Upscaling of [177Lu]Lu-PSMAI&T.

[177Lu]Lu-PSMAI&T is widely used for the radioligand therapy of metastatic castration-resistant prostate cancer (mCRPC). Since this kind of therapy has gained a large momentum in recent years, an upscaled production process yielding multiple patient doses in one batch has been developed. During upscaling, the established production method as well as the HPLC quality control were challenged. A major finding was a correlation between the specific activity and the formation of a pre-peak, presumably caused by radiolysis. Hence, nonradioactive reference standards were irradiated with an X-ray source and the formed pre-peak was subsequently identified as a deiodination product by UPLC-MS. To confirm the occurrence of the same deiodinated side product in the routine batch, a customized deiodinated precursor was radiolabeled and analyzed with the same HPLC setup, revealing an identical retention time to the pre-peak in the formerly synthesized routine batches. Additionally, further cyclization products of [177Lu]Lu-PSMAI&T were identified as major contributors to radiochemical impurities. The comparison of two HPLC methods showed the likelihood of the overestimation of the radiochemical purity during the synthesis of [177Lu]Lu-PSMAI&T. Finally, a prospective cost reduction through an optimization of the production process was shown.

Attenuation correction of a flat table top for radiation therapy in hybrid PET/MR using CT- and 68Ge/68Ga transmission scan-based µ-maps.

Hybrid PET/MR offers new opportunities in radiation oncology for tissue/tumour characterisation and response assessment. Attenuation correction (AC) is an important issue especially in the presence of immobilization devices and flat table tops (FTT). The goal of this study was to compare two methods of AC using CT- and 68Ge/68Ga transmission scan-based attenuation maps (µ-maps) for a custom-designed FTT. Measurements were performed in the mMR PET/MR and TrueV PET/CT Biograph Siemens scanners with three different phantoms, namely the Siemens MR-QA, a cubic canister and the NEMA IEC body phantom. The study revealed that the MR image quality is not hampered by the presence of the FTT. For cubic canister applying the scanner's inherent AC alone resulted in inaccuracies in PET images, with up to -4.0% underestimation of the activity. The mean NEMA sphere activity measurements without FTT, agreed within 3.5% with the respective inserted activity. Placing the FTT in the PET/MR scanner resulted in a difference to the injected activity of 4.5% when the table was not corrected for. By introducing the µ-maps the discrepancy between the used activity and the measurements decreased down to 2.6%. To improve the AC of the FTT the creation of a dedicated µ-map was necessary while the CT-based µ-map performed equally good as the source transmission scan-based one.

Susceptibility-weighted MR imaging in the grading of liver fibrosis: a feasibility study.

PURPOSE: To assess the feasiblity of magnetic resonance (MR) susceptibility-weighted (SW) imaging as a tool to evaluate liver fibrosis grades in patients with chronic liver diseases (CLD) utilizing signal intensity (SI) measurements, with histopathologic findings as the reference standard. MATERIALS AND METHODS: This retrospective study was approved by the local ethics committee. All subjects gave written informed consent. Eighty consecutive patients (mean age, 56.8 years), 60% of whom were male [n = 48] and 40% of whom were female [n = 32], with CLD due to various underlying causes and histopathologically proved liver fibrosis were included. Biopsies were evaluated for liver fibrosis and necroinflammatory activity (according to METAVIR scoring system), iron load, and steatosis. Two radiologists, blinded to the clinical data, assessed regions of interest in the liver and spinal muscle in consensus. Liver-to-muscle SI ratios were calculated and correlated to histopathologic findings and clinical data by using univariate and multivariate regression analysis. RESULTS: Liver-to-muscle SI ratio decreased in parallel with the increasing grade of liver fibrosis and correlated strongly with liver fibrosis (r = -0.81, P < .0001) and moderately with necroinflammatory activity (r = -0.52, P < .0001) and iron load (r = -0.37, P = .0002) but did not correlate with steatosis (r = -0.18, P = .11). In multiple regression analysis, liver fibrosis and iron load independently influenced SW imaging measurements, explaining 69% of the variance of liver-to-muscle SI ratio (R(2) = 0.69, P < .001). Liver-to-muscle SI ratio performed well in grading liver fibrosis, with an area under the receiver operating characteristic curve of 0.92 for scores of F2 or higher and 0.93 for score of F4 (liver cirrhosis). CONCLUSION: SW imaging is a feasible noninvasive tool to detect moderate and advanced liver fibrosis in CLD patients.

Combining phase images from multi-channel RF coils using 3D phase offset maps derived from a dual-echo scan.

A method is presented for the combination of phase images from multi-channel RF coils in the absence of a volume reference coil. It is based on the subtraction of 3D phase offset maps from the phase data from each coil. Phase offset maps are weighted combinations of phase measurements at two echo times. Multi-Channel Phase Combination using measured 3D phase offsets (MCPC-3D) offers a conceptually and computationally simple solution to the calculation of combined phase images. The dual-echo data required for the phase maps can be intrinsic to the high-resolution gradient-echo scan to be reconstructed (MCPC-3D-I). Alternatively, a separate, fast, low-resolution dual-echo scan can be used (MCPC-3D-II). Both variants are shown to give near perfect phase matching, yielding images with high SNR throughout and high GM-WM contrast. MCPC-3D is compared with other reference-free phase image combination methods; high-pass phase filtering, phase difference imaging, and matching using constant offsets (MCPC-C). Multi-Channel Phase Combination using measured 3D phase offsets method does not need an overlap between the signals from individual coils and can be used with parallel imaging, making it ideally suited to multi-channel coils with a large number of elements, and to high and ultra-high field systems.

Phase unwrapping of MR images using Phi UN--a fast and robust region growing algorithm.

We present a fully automated phase unwrapping algorithm (Phi UN) which is optimized for high-resolution magnetic resonance imaging data. The algorithm is a region growing method and uses separate quality maps for seed finding and unwrapping which are retrieved from the full complex information of the data. We compared our algorithm with an established method in various phantom and in vivo data and found a very good agreement between the results of both techniques. Phi UN, however, was significantly faster at low signal to noise ratio (SNR) and data with a more complex phase topography, making it particularly suitable for applications with low SNR and high spatial resolution. Phi UN is freely available to the scientific community.

Susceptibility weighted imaging at ultra high magnetic field strengths: theoretical considerations and experimental results.

We present numerical simulations and experimental results for susceptibility weighted imaging (SWI) at 7 T. Magnitude, phase, and SWI contrast were simulated for different voxel geometries and imaging parameters, resulting in an echo time of 14 msec for optimum contrast between veins and surrounding tissue. Slice thickness of twice the in-plane voxel size or more resulted in optimum vessel visibility. Phantom and in vivo data are in very good agreement with the simulations and the delineation of vessels at 7 T was superior compared to lower field strengths. The phase of the complex data reveals anatomical details that are complementary to the corresponding magnitude images. Susceptibility weighted imaging at very high field strengths is a promising technique because of its high sensitivity to tissue susceptibility, its low specific absorption rate, and the phase's negligible sensitivity to B(1) inhomogeneities.

Improved elimination of phase effects from background field inhomogeneities for susceptibility weighted imaging at high magnetic field strengths.

To enhance susceptibility-related contrast of magnetic resonance images, the phase of susceptibility weighted data needs to be corrected for background inhomogeneities and phase wraps caused by them. Current methods either use homodyne filtering or a combination of phase unwrapping and high pass filtering. The drawback of homodyne filtering is incomplete elimination of phase wraps in areas with steep phase topography produced by background inhomogeneities of the static magnetic field. The disadvantage of phase unwrapping is that it requires subsequent high pass filtering, which introduces artifacts in areas with very steep transitions, such as areas near interfaces between parenchyma and bone or air. A method is proposed that reduces the artifacts associated with high pass filtering without sacrificing the advantages of phase unwrapping. This technique is demonstrated with phantom data at 1.5 T and with human data at 1.5, 3 and 7 T.

Informatics in Radiology: GUIBOLD: a graphical user interface for image reconstruction and data analysis in susceptibility-weighted MR imaging.

Susceptibility-weighted (SW) magnetic resonance (MR) imaging provides high-resolution, distortion-free blood oxygen level-dependent (BOLD) data for assessment of cerebral veins, blood products, and brain lesions. Currently, reconstruction of SW imaging data is not implemented on all MR imaging systems or is restricted in terms of parameter adjustments. New developments in SW imaging have been implemented into a graphical user interface (GUI), which is named GUIBOLD. The GUI was designed for imaging system-independent off-line data reconstruction with interactive setting of parameters on the basis of k-space data and Digital Imaging and Communications in Medicine images. GUIBOLD is capable of presenting magnitude, unwrapped phase, and SW images in different orientations and parallel projections with various rendering methods and region-of-interest-based data analysis tools. Moreover, GUIBOLD affords easy and comprehensive data reconstruction possibilities for venographic and arterial imaging and anatomic phase imaging. As a direct application, differentiation between cavernous and calcified lesions on the basis of their magnetic susceptibility on phase images was performed. GUIBOLD widens the range of potential applications of SW imaging and makes it more accessible for use in the clinical routine as well as in medical research.

Detection of multiple intracranial hemorrhages in a child with acute lymphocytic leukemia (ALL) by susceptibility weighted imaging (SWI).

Susceptibility weighted imaging (SWI) combines magnitude and phase information from a high-resolution, fully velocity compensated, three-dimensional (3D) gradient echo sequence. We report on the use of this MRI technique in a young patient with acute lymphocytic leukemia (ALL) and demonstrate a higher detection rate of hemorrhagic lesion in comparison with other T2*-weighted sequences.

Contrast-enhanced, high-resolution, susceptibility-weighted magnetic resonance imaging of the brain: dose-dependent optimization at 3 tesla and 1.5 tesla in healthy volunteers.

OBJECTIVES: We sought to determine the optimal dose of a contrast agent with known high relaxivity on 1.5 and 3 Tesla scanners that would achieve the best compromise between image quality and scan time for the clinical application of contrast-enhanced susceptibility-weighted imaging (CE-SWI). METHODS: Pre- and postcontrast SWI was performed with different contrast agent doses (0.05, 0.1, and 0.2 mmol/kg gadobenate dimeglumine) at both 1.5 and 3 T in 6 healthy volunteers, resulting in 72 examinations. Venograms were created from minimum intensity projection reconstructions over specified deep white matter volumes to enhance the visual appearance of connected venous structures. Three independent radiologists blindly rated the visibility of the veins on a continuous scale of 1 to 10. A general linear model was used for statistical evaluation, with fixed effects of the contrast agent dose, the field strength, the rater and the patients as a random effect. RESULTS: With CE-SWI, we found significant differences in the visibility of the deep veins dependent on the contrast media dose (P=0.02). At 3 T, the visibility of deep venous vessels, with regard to susceptibility effect, image quality, and scan time reduction after a standard contrast agent dose 0.1 mmol/kg was significantly better than that achieved with 0.05 mmol/kg. The visibility was considered equal with 0.1 mmol/kg of the contrast agent to the precontrast images and a dose of 0.2 mmol/kg. At 1.5 T, no significant difference was found between the 4 contrast agent doses. We found no difference in the visibility of the veins with the shorter sequences at 3 T compared with the sequences at 1.5 T. CONCLUSIONS: Only a standard dose (0.1 mmol/kg) of gadobenate dimeglumine is required to achieve the optimum susceptibility effect and image quality at 3 T, together with a reduced scan time. This result can be attributed to the higher relaxivity of gadobenate dimeglumine, compared with conventional gadolinium chelates.

Demonstration of paramagnetic and diamagnetic cerebral lesions by using susceptibility weighted phase imaging (SWI).

Susceptibility-weighted MR imaging (SWI) has become a non-invasive diagnostic modality for functional MR imaging (fMRI) of the brain and also for the imaging of tumors, injuries, malformations or microhemorrhages. SWI often enables detection of otherwise subtle abnormalities or provides additional relevant information when combined with routine MR imaging. The purpose of this article is to illustrate the potential of SWI in the discrimination of paramagnetic and diamagnetic brain lesions in neuroradiological applications.