Sinonasal mucosal melanoma treatment response assessment to immune checkpoint inhibitors using hybrid positron emission tomography imaging.

The purpose of this retrospective study was to investigate response of sinonasal mucosal melanoma (SMM) patients to treatment with immune checkpoint inhibitors (ICI), using hybrid PET imaging. Fifteen SMM patients underwent hybrid PET imaging before and three months after initiation of ICI. The disease-specific survival (DSS) was calculated. Quantitative PET parameters of the primary tumor and their association with DSS and therapy response were investigated. Nine of the fifteen (60%) patients responded to ICI therapy. Patients with therapy response depicted on hybrid PET imaging had better DSS than those without (p = 0.0058). Quantitative PET parameters of the initial PET harbored no association with DSS or therapy response. However, these findings lack of sufficient statistical power and must be interpreted with caution. The first restaging PET-imaging after ICI initiation can help stratify patients with regard to DSS.

Outcome analysis in patients with metastatic gastroenteropancreatic neuroendocrine tumors receiving peptide receptor radionuclide therapy with Lu-177-DOTATATE.

Background: Patients with neuroendocrine tumors (NET) of the gastroenteropancreatic tract (GEP-NET) were effectively treated with peptide receptor radionuclide therapy (PRRT) with Lu-177-DOTATATE in the NETTER-1 trial. The aim of this study was to assess the outcome of metastatic GEP-NET patients within a European Neuroendocrine Tumor Society (ENETS) certified center of excellence after this treatment. Methods: A total of 41 GEP-NET patients who received PRRT with Lu-177-DOTATATE between 2012 and 2017 at a single center were included in this analysis. Data on pre- and post-PRRT treatments [selective internal radiation therapy (SIRT), somatostatin analogue therapy (SSA), blood parameters, patient symptomatic burden and overall survival] was extracted from patient records. Results: Overall, PRRT was well tolerated and did not increase patient symptomatic burden. Blood parameters were not significantly affected by PRRT (means before and after therapy: hemoglobin: 125.4 vs. 122.3 mg/L, P=0.201; creatinine: 73.8 vs. 77.7 µmol/L, P=0.146), while leukocytes (6.6 vs. 5.6 G/L, P<0.01) and platelets (269.9 vs. 216.7 G/L, P<0.001) were significantly decreased yet without clinical significance in our study. Seven of 9 patients with SIRT treatment prior to PRRT were deceased (mortality odds ratio =4.083). The mortality odds ratio of patients with a pancreatic tumor and SIRT was 1.33 compared to patients with a different tumor origin. 6 of 15 patients (40%) with post-PRRT SSA were deceased (mortality odds ratio =0.429 without SSA after PRRT). Conclusions: Patients with advanced GEP-NET might benefit from PRRT with Lu-177-DOTATATE as it can provide a valuable treatment modality in advanced disease stages. Safety profiles of PRRT were manageable without increasing the symptomatic burden. SIRT before PRRT or lack of SSA after PRRT seem to impair the response and reduce survival.

Radiation dose reduction with deep-learning image reconstruction for coronary computed tomography angiography.

OBJECTIVES: Deep-learning image reconstruction (DLIR) offers unique opportunities for reducing image noise without degrading image quality or diagnostic accuracy in coronary CT angiography (CCTA). The present study aimed at exploiting the capabilities of DLIR to reduce radiation dose and assess its impact on stenosis severity, plaque composition analysis, and plaque volume quantification. METHODS: This prospective study includes 50 patients who underwent two sequential CCTA scans at normal-dose (ND) and lower-dose (LD). ND scans were reconstructed with Adaptive Statistical Iterative Reconstruction-Veo (ASiR-V) 100%, and LD scans with DLIR. Image noise (in Hounsfield units, HU) and quantitative plaque volumes (in mm3) were assessed quantitatively. Stenosis severity was visually categorized into no stenosis (0%), stenosis (< 20%, 20-50%, 51-70%, 71-90%, 91-99%), and occlusion (100%). Plaque composition was classified as calcified, non-calcified, or mixed. RESULTS: Reduction of radiation dose from ND scans with ASiR-V 100% to LD scans with DLIR at the highest level (DLIR-H; 1.4 mSv vs. 0.8 mSv, p < 0.001) had no impact on image noise (28 vs. 27 HU, p = 0.598). Reliability of stenosis severity and plaque composition was excellent between ND scans with ASiR-V 100% and LD scans with DLIR-H (intraclass correlation coefficients of 0.995 and 0.974, respectively). Comparison of plaque volumes using Bland-Altman analysis revealed a mean difference of - 0.8 mm3 (± 2.5 mm3) and limits of agreement between - 5.8 and + 4.1 mm3. CONCLUSION: DLIR enables a reduction in radiation dose from CCTA by 43% without significant impact on image noise, stenosis severity, plaque composition, and quantitative plaque volume. KEY POINTS: •Deep-learning image reconstruction (DLIR) enables radiation dose reduction by over 40% for coronary computed tomography angiography (CCTA). •Image noise remains unchanged between a normal-dose CCTA reconstructed by ASiR-V and a lower-dose CCTA reconstructed by DLIR. •There is no impact on the assessment of stenosis severity, plaque composition, and quantitative plaque volume between the two scans.

A descriptive analysis of the characteristics, treatment response and prognosis of hepatic dominant solid tumors undergoing selective internal radiation therapy (SIRT).

Background: Selective internal radiotherapy is widely used for liver dominant diseases of solid tumors. However, data about sequential treatment and prognostic factors are lacking. Methods: We consecutively included all 209 patients who received a selective internal radiotherapy intervention between January 2015 and May 2019. A retrospective analysis of their electronic patient records was performed regarding diagnosis of cancer, previous therapies and applied radioactive activity. A multicenter follow-up at least 6 weeks after intervention to assess radiological response and irregular subsequent follow-ups to asses disease progression were conducted. In addition, subgroup analyses were carried out. Results: The most frequently treated indications were hepatocellular carcinoma (37%), colorectal cancers (14%), neuroendocrine tumors (9%), and breast cancer (8%). In hepatocellular carcinoma, selective internal radiotherapy was most performed without prior systemic therapy (40%), and for the remaining indications, most often after surgery with systemic therapy in sequence. Local radiological response, defined as either regression or stable disease, was assessed at least 6 weeks after intervention and showed 52% across all indications. Hepatocellular carcinoma (59%) and breast cancer (67%) showed an excellent, colorectal cancers (29%) a particularly poor response rate. Neuroendocrine tumors showed the third longest median post-selective internal radiation therapy (SIRT) survival with 12.4 months and the second longest median progression-free time with 5.2 months. Hepatocellular carcinoma showed even better results with a post-SIRT survival of 15.7 months and a median progression-free time of 5.3 months. Pancreatic neuroendocrine tumors showed significantly worse outcomes than other neuroendocrine tumors, regarding median post-SIRT survival and median progression-free time. No relevant SIRT related differences among sexes were detected. Conclusions: Patients with neuroendocrine tumors, breast cancer in late therapy lines and early-stage hepatocellular carcinoma seem to show better responses to SIRT than other entities. Colorectal cancers were mainly treated with SIRT in a second or third therapy line but with considerably weaker results than other entities.

Prognostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine PET in relapsing oligodendroglioma.

PURPOSE: To assess the relationship between F-18-fluoro-ethyl-tyrosine positron emission tomography (FET-PET) parameters of relapsing oligodendroglioma and progression-free survival. MATERIAL AND METHODS: The relationship of clinical parameters, FET-PET parameters (SUVmax, TBRmax, BTV, time-activity curves) and progression-free survival was analyzed using univariate and multivariate analysis in 42 adult patients with relapsing oligodendroglioma. Kaplan-Meier analysis was used to assess survival. RESULTS: Patients who did not undergo surgical resection of their relapsing tumor had significantly lower PFS if the tumor exhibited an SUVmax above 3.40 than those with an SUVmax below 3.40 (13.1 ± 2.3 months vs. 47.3 ± 6.0 months, respectively, p < .001). Patients who underwent surgery had similar PFS as the aforementioned non-operated patients with low SUVmax (53.6 ± 6.7 months, p = .948). The same was true for TBRmax using a threshold of 3.03 (PFS 12.5 ± 2.4 months vs. 44.0 ± 6.3 months / 53.6 ± 6.7 months, respectively; p < .001 / p = .825). Also, subjects with BTV below 10 cm3 that did not undergo surgery had a similar PFS as subjects who underwent surgery (40.2 ± 6.0 months vs. 52.4 ± 8.9 months, respectively, p = .587). Subjects with BTV above 10 cm3 and without surgery had a significantly worse PFS (13.8 ± 3.3 months, p < .001). Multivariate analysis showed that the prognostication by clinical parameters is improved by adding TBRmax to the model (AUC 0.945 (95% CI: 0.881-1.000), true classification rate 88.1%). CONCLUSION: FET-PET may provide added value for the prognostication of relapsing oligodendroglioma in addition to clinical parameters.

Outpatient Yttrium-90 microsphere radioembolization: assessment of radiation safety and quantification of post-treatment adverse events causing hospitalization.

PURPOSE: Quantification of post-interventional adverse events of outpatient SIRT leading to hospitalization and quantification of radiation exposure. MATERIALS AND METHODS: In this single-center, retrospective cohort study, we reviewed 212 patients treated with SIRT (90Y-microspheres) for primary and secondary liver malignancies. We searched for adverse events (AEs) and serious adverse events (SAEs), defined as AE's causing hospitalization. Additionally, radiation exposure was measured in 36 patients. RESULTS: Seven patients had an SAE (3.3%), four patients had AE without readmission/hospitalization (1.9%) and 201 patients had no complications (94.8%). The mean ambient dose rate at 1 m distance from the source after administration of 90Y-microspheres was 1.88 µSv/h ± 0.74 (± SD) with a range from 4.3 to 0.2 µSv/h. CONCLUSION: Outpatient radioembolization with 90Y-microspheres is safe and requires hospitalization only in a very small number of patients. The mean dose rate was low and met the national conditions for outpatient treatment (< 5 µSv/h).

Impact of different image reconstructions on PET quantification in non-small cell lung cancer: a comparison of adenocarcinoma and squamous cell carcinoma.

OBJECTIVE:: Positron emission tomography (PET) using 18F-fludeoxyglucose (18F-FDG) is an established imaging modality for tumor staging in patients with non-small cell lung cancer (NSCLC). There is a growing interest in using 18F-FDG PET for therapy response assessment in NSCLC which relies on quantitative PET parameters such as standardized uptake values (SUV). Different reconstruction algorithms in PET may affect SUV. We sought to determine the variation of SUV in patients with NSCLC when using ordered subset expectation maximization (OSEM) and block sequential regularized expectation maximization (BSREM) in latest-generation digital PET/CT, including a subanalysis for adenocarcinoma and squamous cell carcinoma. METHODS:: A total of 58 patients (34 = adenocarcinoma, 24 = squamous cell carcinoma) who underwent a clinically indicated 18F-FDG PET/CT for staging were reviewed. PET images were reconstructed with OSEM and BSREM reconstruction with noise penalty strength ß-levels of 350, 450, 600, 800 and 1200. Lung tumors maximum standardized uptake value (SUVmax) were compared. RESULTS:: Lung tumors SUVmax were significantly lower in adenocarcinomas compared to squamous cell carcinomas in all reconstructions evaluated (all p < 0.01). Comparing BSREM to OSEM, absolute SUVmax differences were highest in lower ß-levels of BSREM with + 2.9 ± 1.6 in adenocarcinoma and + 4.0 ± 2.9 in squamous cell carcinoma (difference between histology; p-values > 0.05). There was a statistically significant difference of the relative increase of SUVmax in adenocarcinoma (mean + 34.8%) and squamous cell carcinoma (mean 23.4%), when using BSREM350 instead of OSEMTOF (p < 0.05). CONCLUSION:: In NSCLC the relative change of SUV when using BSREM instead of OSEM is significantly higher in adenocarcinoma as compared to squamous cell carcinoma. ADVANCES IN KNOWLEDGE:: The impact of BSREM on SUV may vary in different histological subtypes of NSCLC. This highlights the importance for careful standardization of ß-value used for serial 18F-FDG PET scans when following-up NSCLC patients.

A Micro CT Study in Patients with Breast Microcalcifications Using a Mathematical Algorithm to Assess 3D Structure.

PURPOSE: The aim of this study was to evaluate the relevance of the three-dimensional (3D) structure of breast microcalcifications (MC) as a predictor of malignancy using highly resolved micro-computed tomography (micro-CT) datasets of biopsy samples. MATERIAL AND METHODS: The study included 28 women with suspicious MC in their mammogram undergoing vacuum-assisted biopsy. Directly after the intervention, the specimens were scanned in a micro-CT with an isometric spatial resolution of 9 µm. Datasets were analysed regarding the number, volume and morphology of suspicious non-monomorphic MC (fl-fine linear, fp-fine pleomorphic, ch-coarse heterogeneous) and the structure model index (SMI). Histological evaluation was performed according to the B-classification: normal tissue or benign (group A: B1, B2), unclear malignant potential or suspicious of malignancy (group B: B3, B4) and malignant lesions (group C: B5). RESULTS: In all groups, suspicious non-monomorphic MC were found: group A exhibited fp MC in 38.5% of samples, no fl/ch; group B: fl 14.3%, fp 28.6%, ch 14.3%; group C always had at least one type of suspicious non-monomorphic MC (fl (57.1%) or fp (57.1%)) in each sample. The different histologic groups showed a similar mean SMI (benign: 2.97 ± 0.31, malignant: 3.02 ± 0.10, unclear: 2.90 ± 0.28). Between the three groups, no significant differences were found regarding number, volume or SMI value of MC. CONCLUSION: 3D structure based on the SMI of MC analysed with highest spatial resolution is not significantly associated with the B-classification of breast lesions. Thus, magnification views of MC may be omitted in the analysis of MC detected in mammograms.

Neer Award 2016: reduced muscle degeneration and decreased fatty infiltration after rotator cuff tear in a poly(ADP-ribose) polymerase 1 (PARP-1) knock-out mouse model.

BACKGROUND: Disturbed muscular architecture, atrophy, and fatty infiltration remain irreversible in chronic rotator cuff tears even after repair. Poly (adenosine 5'-diphosphate-ribose) polymerase 1 (PARP-1) is a key regulator of inflammation, apoptosis, muscle atrophy, muscle regeneration, and adipocyte development. We hypothesized that the absence of PARP-1 would lead to a reduction in damage to the muscle subsequent to combined tenotomy and neurectomy in a PARP-1 knockout (KO) mouse model. METHODS: PARP-1 KO and wild-type C57BL/6 (WT group) mice were analyzed at 1, 6, and 12 weeks (total n = 84). In all mice, the supraspinatus and infraspinatus muscles of the left shoulder were detached and denervated. Macroscopic analysis, magnetic resonance imaging, gene expression analysis, immunohistochemistry, and histology were used to assess the differences in PARP-1 KO and WT mice. RESULTS: The muscles in the PARP-1 KO group had significantly less retraction, atrophy, and fatty infiltration after 12 weeks than in the WT group. Gene expression of inflammatory, apoptotic, adipogenic, and muscular atrophy genes was significantly decreased in PARP-1 KO mice in the first 6 weeks. DISCUSSION: Absence of PARP-1 leads to a reduction in muscular architectural damage, early inflammation, apoptosis, atrophy, and fatty infiltration after combined tenotomy and neurectomy of the rotator cuff muscle. Although the macroscopic reaction to injury is similar in the first 6 weeks, the ability of the muscles to regenerate was much greater in the PARP-1 KO group, leading to a near-normalization of the muscle after 12 weeks.

Simultaneous Multislice Diffusion-Weighted Imaging of the Kidney: A Systematic Analysis of Image Quality.

OBJECTIVES: The aims of this study were to implement a protocol for simultaneous multislice (SMS) accelerated diffusion-weighted imaging (DWI) of the kidneys and to perform a systematic analysis of image quality of the data sets. MATERIALS AND METHODS: Ten healthy subjects and 5 patients with renal masses underwent DWI of the kidney in this prospective institutional review board-approved study on a 3 T magnetic resonance scanner. Simultaneous multislice DWI echo-planar sequences (acceleration factors [AFs] 2 and 3) were compared with conventional echo-planar DWI as reference standard for each acquisition scheme. The following 3 acquisition schemes were applied: comparison A, with increased number of acquisitions at constant scan time; comparison B, with reduction of acquisition time; and comparison C, with increased slice resolution (constant acquisition time, increasing number of slices). Interreader reliability was analyzed by calculating the intraclass correlation coefficient (ICC). Qualitative image quality features were evaluated by 2 independent radiologists on a 5-point Likert scale. Quantification accuracy of the apparent diffusion coefficients (ADCs) and signal-to-noise ratios (SNRs) were assessed by region of interest analysis. Furthermore, lesion conspicuity in the 5 patients was assessed using a 5-point Likert scale by 2 independent radiologists. RESULTS: Interreader agreement was substantial with an ICC of 0.68 for the overall image quality and an ICC of 0.73 for the analysis of artifacts. In comparison A, AF2 resulted in increased SNR (P < 0.05) by 21% at stable image quality scores (image quality: P = 0.76, artifacts: P = 0.21). In comparison B, applying AF2, the scan time could be reduced by 46% without significant reduction in qualitative image quality scores (P = 0.059) or SNR (P = 0.126). In comparison C, slice resolution could be improved by 28% using AF2 with stable image quality scores and SNR. In general, AF3 resulted in reduced image quality and SNR. Significantly reduced ADC values were observed for AF3 in comparison C (cortex: P = 0.003; medulla: P = 0.001) compared with the standard echo-planar imaging sequence. The conventional DWI and the SMS DWI with AF2 showed stable lesion conspicuity ([AF1/AF2]: reader 1 [1.8/1.4] and reader 2 [1.8/1.4]). The lesion conspicuity was lower using AF3 (reader 1: 2.2 and reader 2: 1.8). CONCLUSIONS: In conclusion, SMS DWI of the kidney is a potential tool to substantially reduce scan time without negative effects on SNR, ADC quantification accuracy, and image quality if an AF2 is used. Although AF3 results in even higher scan time reduction, a negative impact on image quality, SNR, ADC quantification accuracy, and lesion conspicuity must be considered.

Magnetization transfer as a potential tool for the early detection of acute graft rejection after lung transplantation in mice.

PURPOSE: To investigate the value of magnetization transfer (MT) measurements for assessment of acute rejection (AR) in a murine lung transplantation model. MATERIALS AND METHODS: Thirty mice including 15 C57BL/10 mice serving as donors and 15 C57BL/6 mice as recipients were examined in this study. MT imaging datasets were acquired on a 4.7 Tesla small animal MR scanner using a three-dimensional zero echo time sequence with a Gaussian-shaped MT prepulse with 1000° or 3000° flip angle and systematic variation of off-resonance frequencies between 1000 and 15,000 Hz. After image acquisition, the images were qualitatively assessed, magnetization transfer ratio (MTR) values were calculated and lungs were taken for histologic examination including staining with hematoxylin/eosin, Masson's trichrome (collagen), and α-smooth muscle (fibroproliferative tissue) staining. RESULTS: Lung transplantation was successfully performed in all 15 mice. All animals showed AR characterized by the presence of interstitial mononuclear cell infiltrates. There were significant differences of MTR in lungs with and without AR (P = 0.007). With a flip angle of 1000°, the largest differences between the MTR of healthy lungs and lungs with AR were observed for an off-resonance frequency of 10,000 Hz (difference MTR 1.80%) and 15,000 Hz (1.91%) and with a flip angle of 3000° at off-resonance frequencies of 6000 Hz (1.37%) and 8000 Hz (1.70%). CONCLUSION: MT measurements may provide a tool for the quantitative assessment of AR. J. Magn. Reson. Imaging 2016;44:1091-1098.

Antagonizing the Hedgehog Pathway with Vismodegib Impairs Malignant Pleural Mesothelioma Growth In Vivo by Affecting Stroma.

An autocrine-driven upregulation of the Hedgehog (Hh) signaling pathway has been described in malignant pleural mesothelioma (MPM), in which the ligand, desert Hh (DHH), was produced from tumor cells. However, our investigation revealed that the Hh pathway is activated in both tumor and stroma of MPM tumor specimens and an orthotopic immunocompetent rat MPM model. This was demonstrated by positive immunohistochemical staining of Glioma-associated oncogene 1 (GLI1) and Patched1 (PTCH1) in both tumor and stromal fractions. DHH was predominantly expressed in the tumor fractions. To further investigate the role of the Hh pathway in MPM stroma, we antagonized Hh signaling in the rat model of MPM using a Hh antagonist, vismodegib, (100 mg/kg orally). Daily treatment with vismodegib efficiently downregulated Hh target genes Gli1, Hedgehog Interacting Protein (Hhip), and Ptch1, and caused a significant reduction of tumor volume and tumor growth delay. Immunohistochemical analyses revealed that vismodegib treatment primarily downregulated GLI1 and HHIP in the stromal compartment along with a reduced expression of previously described fibroblast Hh-responsive genes such as Fibronectin (Fn1) and Vegfa Primary cells isolated from the rat model cultured in 3% O2 continued to express Dhh but did not respond to vismodegib in vitro However, culture supernatant from these cells stimulated Gli1, Ptch1, and Fn1 expression in mouse embryonic fibroblasts, which was suppressed by vismodegib. Our study provides new evidence regarding the role of Hh signaling in MPM stroma in the maintenance of tumor growth, emphasizing Hh signaling as a treatment target for MPM. Mol Cancer Ther; 15(5); 1095-105. ©2016 AACR.

Simultaneous multi-slice readout-segmented echo planar imaging for accelerated diffusion-weighted imaging of the breast.

OBJECTIVES: Readout-segmented echo planar imaging (rs-EPI) significantly reduces susceptibility artifacts in diffusion-weighted imaging (DWI) of the breast compared to single-shot EPI but is limited by longer scan times. To compensate for this, we tested a new simultaneous multi-slice (SMS) acquisition for accelerated rs-EPI. MATERIALS AND METHODS: After approval by the local ethics committee, eight healthy female volunteers (age, 38.9 ± 13.1 years) underwent breast MRI at 3T. Conventional as well as two-fold (2× SMS) and three-fold (3× SMS) slice-accelerated rs-EPI sequences were acquired at b-values of 50 and 800 s/mm(2). Two independent readers analyzed the apparent diffusion coefficient (ADC) in fibroglandular breast parenchyma. The signal-to-noise ratio (SNR) was estimated based on the subtraction method. ADC and SNR were compared between sequences by using the Friedman test. RESULTS: The acquisition time was 4:21 min for conventional rs-EPI, 2:35 min for 2× SMS rs-EPI and 1:44 min for 3× SMS rs-EPI. ADC values were similar in all sequences (mean values 1.62 × 10(-3)mm(2)/s, p=0.99). Mean SNR was 27.7-29.6, and no significant differences were found among the sequences (p=0.83). CONCLUSION: SMS rs-EPI yields similar ADC values and SNR compared to conventional rs-EPI at markedly reduced scan time. Thus, SMS excitation increases the clinical applicability of rs-EPI for DWI of the breast.

Functional Characterization of Germline Mutations in PDGFB and PDGFRB in Primary Familial Brain Calcification.

Primary Familial Brain Calcification (PFBC), a neurodegenerative disease characterized by progressive pericapillary calcifications, has recently been linked to heterozygous mutations in PDGFB and PDGFRB genes. Here, we functionally analyzed several of these mutations in vitro. All six analyzed PDGFB mutations led to complete loss of PDGF-B function either through abolished protein synthesis or through defective binding and/or stimulation of PDGF-Rß. The three analyzed PDGFRB mutations had more diverse consequences. Whereas PDGF-Rß autophosphorylation was almost totally abolished in the PDGFRB L658P mutation, the two sporadic PDGFRB mutations R987W and E1071V caused reductions in protein levels and specific changes in the intensity and kinetics of PLCγ activation, respectively. Since at least some of the PDGFB mutations were predicted to act through haploinsufficiency, we explored the consequences of reduced Pdgfb or Pdgfrb transcript and protein levels in mice. Heterozygous Pdgfb or Pdgfrb knockouts, as well as double Pdgfb+/-;Pdgfrb+/- mice did not develop brain calcification, nor did Pdgfrbredeye/redeye mice, which show a 90% reduction of PDGFRß protein levels. In contrast, Pdgfbret/ret mice, which have altered tissue distribution of PDGF-B protein due to loss of a proteoglycan binding motif, developed brain calcifications. We also determined pericyte coverage in calcification-prone and non-calcification-prone brain regions in Pdgfbret/ret mice. Surprisingly and contrary to our hypothesis, we found that the calcification-prone brain regions in Pdgfbret/ret mice model had a higher pericyte coverage and a more intact blood-brain barrier (BBB) compared to non-calcification-prone brain regions. While our findings provide clear evidence that loss-of-function mutations in PDGFB or PDGFRB cause PFBC, they also demonstrate species differences in the threshold levels of PDGF-B/PDGF-Rß signaling that protect against small-vessel calcification in the brain. They further implicate region-specific susceptibility factor(s) in PFBC pathogenesis that are distinct from pericyte and BBB deficiency.

Evaluation of imaging techniques for the assessment of tumour progression in an orthotopic rat model of malignant pleural mesothelioma†.

OBJECTIVES: An orthotopic rat tumour recurrence model for malignant pleural mesothelioma (MPM) provides clinical similarity to patients and is useful for drug testing combined with surgical intervention. Importantly, a reliable imaging method is required allowing for noninvasive and repetitive evaluation of the tumour load. We compared the tumour load assessed by bioluminescence and magnetic resonance imaging (MRI) to the macroscopic tumour volume as a reference standard. METHODS: A total of 500,000 syngeneic rat MPM cells transfected with luciferase were implanted underneath the parietal pleura of immunocompetent rats (n=13). From the second day after implantation, bioluminescence measurements of the tumour load expressed as the maximum bioluminescent intensity (photon/second) were performed daily after intraperitoneal injection of the luciferase substrate, d-luciferin, to observe the first occurrence of tumour. Six days after the first detection of tumour, bioluminescence, MRI and macroscopic tumour volume measurement were conducted. For MRI, a 4.7-Tesla small animal imager equipped with a 1H whole-body rat coil was employed using T2-weighted fast spin-echo sequences. Tumour burden (mm3) was quantified from magnetic resonance transverse images by two independent readers by manual segmentation. Finally, the tumour burden assessed by bioluminescence and MRI was correlated (Pearson's correlation) with the macroscopic measurement of tumour (ellipsoid) volume. RESULTS: In all rats, a single tumour nodule was found at the inoculation site with a median macroscopic volume of 46 mm3 (18-377 mm3). For tumour burden quantification of MRIs, we observed good interobserver correlation (R2=0.81, P<0.0001) as well as significant association with the macroscopic tumour volume (R2=0.59, P=0.002). However, the signal intensity of bioluminescence did not correspond to the macroscopic tumour volume (R2=0.01, P=0.76). CONCLUSIONS: MRI is a reliable and reproducible noninvasive in vivo imaging method for MPM tumour burden assessment for the present MPM model.

Hybrid PET/MR imaging: an algorithm to reduce metal artifacts from dental implants in Dixon-based attenuation map generation using a multiacquisition variable-resonance image combination sequence.

UNLABELLED: It was the aim of this study to implement an algorithm modifying Dixon-based MR imaging datasets for attenuation correction in hybrid PET/MR imaging with a multiacquisition variable resonance image combination (MAVRIC) sequence to reduce metal artifacts. METHODS: After ethics approval, in 8 oncologic patients with dental implants data were acquired in a trimodality setup with PET/CT and MR imaging. The protocol included a whole-body 3-dimensional dual gradient-echo sequence (Dixon) used for MR imaging-based PET attenuation correction and a high-resolution MAVRIC sequence, applied in the oral area compromised by dental implants. An algorithm was implemented correcting the Dixon-based µ maps using the MAVRIC in areas of Dixon signal voids. The artifact size of the corrected µ maps was compared with the uncorrected MR imaging µ maps. RESULTS: The algorithm was robust in all patients. There was a significant reduction in mean artifact size of 70.5% between uncorrected and corrected µ maps from 697 ± 589 mm(2) to 202 ± 119 mm(2) (P = 0.016). CONCLUSION: The proposed algorithm could improve MR imaging-based attenuation correction in critical areas, when standard attenuation correction is hampered by metal artifacts, using a MAVRIC.

Characterization of trabecular bone density with ultra-short echo-time MRI at 1.5, 3.0 and 7.0 T--comparison with micro-computed tomography.

The goal of this study was to test the potential of ultra-short echo-time (UTE) MRI at 1.5, 3.0 and 7.0 T for depiction of trabecular bone structure (of the wrist bones), to evaluate whether T2* relaxation times of bone water and parametric maps of T2* of trabecular bone could be obtained at all three field strengths, and to compare the T2* relaxation times with structural parameters obtained from micro-computed tomography (micro-CT) as a reference standard. Ex vivo carpal bones of six wrists were excised en bloc and underwent MRI at 1.5, 3.0 and 7.0 T in a whole-body MR imager using the head coil. A three-dimensional radial fat-suppressed UTE sequence was applied with subsequent acquisitions, with six different echo times TE of 150, 300, 600, 1200, 3500 and 7000 µs. The T2* relaxation time and pixel-wise computed T2* parametric maps were compared with a micro-computed-tomography reference standard providing trabecular bone structural parameters including porosity (defined as the bone-free fraction within a region of interest), trabecular thickness, trabecular separation, trabecular number and fractal dimension (Dk). T2* relaxation curves and parametric maps could be computed from datasets acquired at all field strengths. Mean T2* relaxation times of trabecular bone were 4580 ± 1040 µs at 1.5 T, 2420 ± 560 µs at 3.0 T and 1220 ± 300 µs at 7.0 T, when averaged over all carpal bones. A positive correlation of T2* with trabecular bone porosity and trabecular separation, and a negative correlation of T2* relaxation time with trabecular thickness, trabecular number and fractal dimension, was detected (p < 0.01 for all field strengths and micro-CT parameters). We conclude that UTE MRI may be useful to characterize the structure of trabecular bone, comparable to micro-CT.