Role of magnetic resonance imaging for preoperative prediction of early biochemical failure in localized prostate cancer.

Background: The purpose of our study was to assess preoperative clinical biological and Magnetic Resonance Imaging (MRI) predictive factors of early biochemical failure (BF), defined as persistence of significant post-operative plasmatic prostate specific antigen (PSA) level after radical prostatectomy (RP) in patients with localized prostate cancer (PCa). Methods: In a retrospective cohort study we included 142 patients from our university hospital with newly diagnosed PCa, who underwent 3T multiparametric MRI prior to RP. Only the MRI target lesions [Prostate Imaging Reporting and Data System (PIRADS) ≥3] with histological correspondence were considered significant. Clinical, biological, MRI and pathological preoperative data were studied. We performed univariate and multivariate logistic regression analysis to identify significant parameters associated with early BF. Results: Early BF occurred in 14% of patients (20/142). Patients with BF had higher PSA level at diagnosis, Gleason score, number of positive biopsies, size of the largest positive biopsy and higher National Comprehensive Cancer Network (NCCN) risk score (P<0.001 for all). According to MRI, they also had higher T stage and a higher size of capsular contact (P<0.001 for all). In contrast, there was no difference concerning neither ADC value, perfusion profile and zonal location of the index lesion. In multivariate analysis, the best combination of predictive factors of early BF was the association of preoperative Gleason score ≥4+3 [odds ratio (OR) =6.8 (1.4-32.5); P=0.002] and T stage ≥3 on preoperative MRI [OR =17.4 (3.2-94.9); P<0.001] with an area under the curve (AUC) of 0.89 [99% confidence interval (CI): 0.77-1], a negative predictive value of 94% and a positive predictive value of 75%. Conclusions: Combination of simple preoperative biomarkers as Gleason score and T stage according to MRI accurately stratify the risk of early BF following RP. These results emphasize the pivotal role of preoperative MRI for the management of localized PCa.

A Practical Quality Assurance Procedure for Data Acquisitions in Preclinical Simultaneous PET/MR Systems.

The availability of preclinical simultaneous PET/MR imaging systems has been increasing in recent years. Therefore, this technique is progressively moving from the hands of pure physicists towards those of scientists more involved in pharmacology and biology. Unfortunately, these combined scanners can be prone to artefacts and deviation of their characteristics under the influence of external factors or mutual interference between subsystems. This may compromise the image quality as well as the quantitative aspects of PET and MR data. Hence, quality assurance is crucial to avoid loss of animals and experiments. A possible risk to the acceptance of quality control by preclinical teams is that the complexity and duration of this quality control are increased by the addition of MR and PET tests. To avoid this issue, we have selected over the past 5 years, simple tests that can be easily and quickly performed each day before starting an animal PET/MR acquisition. These tests can be performed by the person in charge of the experiment even if this person has a limited expertise in instrumentation and performance evaluation. In addition to these daily tests, other tests are suggested for an advanced system follow-up at a lower frequency. In the present paper, the proposed tests are sorted by periodicity from daily to annual. Besides, we have selected test materials that are available at moderate cost either commercially or through 3D printing.

Prediction of prostate cancer recurrence after radiation therapy using multiparametric magnetic resonance imaging and spectroscopy: assessment of prognostic factors on pretreatment imaging.

Background: To assess whether data from pre-therapeutic multiparametric magnetic resonance imaging (mpMRI) combined with three-dimensional magnetic resonance spectroscopy (3D MRS) provide prognostic factors of biochemical relapse in patients with localized prostate cancer treated by external radiotherapy or brachytherapy. Methods: In our single institution observational retrospective study we included a cohort of 230 patients treated by external radiotherapy or brachytherapy who had an initial mpMRI with 3D MRS from January 2008 to December 2015 for newly diagnosed localized prostatic cancer, proven histologically. Three trained radiologists recorded tumor characteristics, MRI T-stage and metabolic abnormalities from 3D MRS data. Univariate and multivariate Cox analyzes explored the relationship between clinical and imaging variables to highlight prognostic factors for recurrence, using biochemical relapse as the primary endpoint. Results: mpMRI data analysis allowed to reclassify 21.7% of the patients in a MRI National Comprehensive Cancer Network (NCCN) group higher than their initial clinical T-stage, but also to detect a lesion in 78% of the patients considered as clinically T1c. After a median of follow-up of 8.7 years (IQR, 6.6-10.1) following cancer diagnosis, 36 (16%) patients developed a biochemical relapse. The multivariate Cox analysis demonstrated the existence of 3 independent factors for prediction of biochemical recurrence: extracapsular extension (ECE) (HR =3.33; 95% CI: 1.93-5.73; P<0.01), choline/citrate ratio in healthy tissue in the transition zone (TZ) (HR =2.96; 95% CI: 1.06-8.28; P=0.04) and the NCCN Magnetic Resonance Imaging classification (intermediate versus low-risk, HR =3.06; 95% CI: 1.13-8.30; P<0.01). Conclusions: Combination of mpMRI and 3DMRS could aid in the prognostic stratification of localized prostate cancer treated by radiotherapy or brachytherapy, by combining accurate evaluation of tumor extension, and quantification of prostate metabolism.

Characterisation of a split gradient coil design induced systemic imaging artefact on 0.35 T MR-linac systems.

Objective. The aim of this work was to highlight and characterize a systemic 'star-like' artefact inherent to the low field 0.35 T MRIdian MR-linac system, a magnetic resonance guided radiotherapy device. This artefact is induced by the original split gradients coils design. This design causes a surjection of the intensity gradient inZ(or head-feet) direction. This artefact appears on every sequence with phase encoding in the head-feet direction.Approach. Basic gradient echo sequence and clinical mandatory bSSFP sequence were used. Three setups using manufacturer provided QA phantoms were designed: two including the linearity control grid used for the characterisation and a third including two homogeneity control spheres dedicated to the artefact management in a more clinical like situation. The presence of the artefact was checked in four different MRidian sites. The tested parameters based on the literature were: phase encoding orientation, slab selectivity, excitation bandwidth (BWRF), acceleration factor (R) and phase/slab oversampling (PO/SO).Main results. The position of this artefact is constant and reproducible over the tested MRIdian sites. The typical singularity saturated dot or star is visible even with the 3D slab-selection enabled. A management is proposed by decreasing the BWRF, theRin head-feet direction and increasing the PO/SO. The oversampling can be optimized using a formula to anticipate the location of artefact in the field of view.Significance. The star-like artefact has been well characterised. A manageable solution comes at the cost of acquisition time. Observed in clinical cases, the artefact may degrade the images used for the RT planning and repositioning during the treatment unless corrected.

Superparamagnetic Iron Oxide Nanoparticles for Immunotherapy of Cancers through Macrophages and Magnetic Hyperthermia.

Cancer immunotherapy has tremendous promise, but it has yet to be clinically applied in a wider variety of tumor situations. Many therapeutic combinations are envisaged to improve their effectiveness. In this way, strategies capable of inducing immunogenic cell death (e.g., doxorubicin, radiotherapy, hyperthermia) and the reprogramming of the immunosuppressive tumor microenvironment (TME) (e.g., M2-to-M1-like macrophages repolarization of tumor-associated macrophages (TAMs)) are particularly appealing to enhance the efficacy of approved immunotherapies (e.g., immune checkpoint inhibitors, ICIs). Due to their modular construction and versatility, iron oxide-based nanomedicines such as superparamagnetic iron oxide nanoparticles (SPIONs) can combine these different approaches in a single agent. SPIONs have already shown their safety and biocompatibility and possess both drug-delivery (e.g., chemotherapy, ICIs) and magnetic capabilities (e.g., magnetic hyperthermia (MHT), magnetic resonance imaging). In this review, we will discuss the multiple applications of SPIONs in cancer immunotherapy, focusing on their theranostic properties to target TAMs and to generate MHT. The first section of this review will briefly describe immune targets for NPs. The following sections will deal with the overall properties of SPIONs (including MHT). The last section is dedicated to the SPION-induced immune response through its effects on TAMs and MHT.

[123I]MIBG is a better early marker of anthracycline cardiotoxicity than [18F]FDG: a preclinical SPECT/CT and simultaneous PET/MR study.

BACKGROUND: During anthracycline treatment of cancer, there is a lack for biomarkers of cardiotoxicity besides the cardiac dysfunction. The objective of the present study was to compare [18F]FDG and [123I]MIBG (metaiodobenzylguanidine) in a longitudinal study in a doxorubicin-induced cardiotoxicity rat model. METHODS: Male Wistar Han rats were intravenously administered 3 times at 10 days' interval with saline or doxorubicin (5 mg/kg). [123I]MIBG SPECT/CT (single photon emission computed tomography-computed tomography) and simultaneous [18F]FDG PET (positron emission tomography)/7 Tesla cardiac MR (magnetic resonance) imaging acquisitions were performed at 24 h interval before first doxorubicin / saline injection and every 2 weeks during 6 weeks. At 6 weeks, the heart tissue was collected for histomorphometry measurements. RESULTS: At week 4, left ventricle (LV) end-diastolic volume was significantly reduced in the doxorubicin group. At week 6, the decreased LV end-diastolic volume was maintained, and LV end-systolic volume was increased resulting in a significant reduction of LV ejection fraction (47 ± 6% vs. 70 ± 3%). At weeks 4 and 6, but not at week 2, myocardial [18F]FDG uptake was decreased compared with the control group (respectively, 4.2 ± 0.5%ID/g and 9.2 ± 0.8%ID/g at week 6). Moreover, [18F]FDG cardiac uptake correlated with cardiac function impairment. In contrast, from week 2, a significant decrease of myocardial [123I]MIBG heart to mediastinum ratio was detected in the doxorubicin group and was maintained at weeks 4 and 6 with a 45.6% decrease at week 6. CONCLUSION: This longitudinal study precises that after doxorubicin treatment, cardiac [123I]MIBG uptake is significantly reduced as early as 2 weeks followed by the decrease of the LV end-diastolic volume and [18F]FDG uptake at 4 weeks and finally by the increase of LV end-systolic volume and decrease of LV ejection fraction at 6 weeks. Cardiac innervation imaging should thus be considered as an early key feature of anthracycline cardiac toxicity.

Three-dimensional nuclear magnetic resonance spectroscopy: a complementary tool to multiparametric magnetic resonance imaging in the identification of aggressive prostate cancer at 3.0T.

BACKGROUND: The limitations of the assessment of tumor aggressiveness by Prostate Imaging Reporting and Data System (PI-RADS) and biopsies suggest that the diagnostic algorithm could be improved by quantitative measurements in some chosen indications. We assessed the tumor high-risk predictive performance of 3.0 Tesla (3.0T) multiparametric magnetic resonance imaging (mp-MRI) combined with nuclear magnetic resonance spectroscopic sequences (NMR-S) in order to show that the metabolic analysis could bring out an evocative result for the aggressive form of prostate cancer. METHODS: We conducted a retrospective study of 26 patients (mean age, 62.4 years) who had surgery for prostate cancer between 2009 and 2016 after pre-therapeutic assessment with 3.0T mp-MRI and NMR-S. Groups within the intermediate range of the D'Amico risk classification were divided into two categories, low risk (n=20) and high risk (n=6), according to the International Society of Urological Pathology (ISUP) 2-3 limit. Histoprognostic discordances within various risk groups were compared with the corresponding predictive MRI values. The performance of predictive models was assessed based on sensitivity, specificity, and the area under the curve (AUC) of receiver operating characteristic (ROC) curves. RESULTS: After prostatectomy, histological analysis reclassified 18 patients as high-risk, including 16 who were T3 MRI grade, of whom 13 (81.3%) were found to be pT3. Among the patients who had cT1 or cT2 digital rectal examinations, the T3 MRI factor multiplied by 8.7 [odds ratio (OR), 8.7; 95% confidence interval (CI), 1.3-56.2; P=0.024] the relative risk of being pT3 and by 5.8 (OR, 5.8; 95% CI, 0.95-35.7; P=0.05) the relative risk of being pGleason (pGS) > GS-prostate biopsy. Spectroscopic data showed that the choline concentration was significantly higher (P=0.001) in aggressive disease. CONCLUSIONS: The predictive model of tumor aggressiveness combining mp-MRI plus NMR-S was better than the mp-MRI model alone (AUC, 0.95 vs. 0.86). Information obtained by mp-MRI coupled with spectroscopy may improve the detection of occult aggressive disease, helping in the discrimination of intermediate risks.

Performance Evaluation and Compatibility Studies of a Compact Preclinical Scanner for Simultaneous PET/MR Imaging at 7 Tesla.

We present the design and performance of a new compact preclinical system combining positron emission tomography (PET) and magnetic resonance imaging (MRI) for simultaneous scans. The PET contains sixteen SiPM-based detector heads arranged in two octagons and covers an axial field of view (FOV) of 102.5 mm. Depth of interaction effects and detector's temperature variations are compensated by the system. The PET is integrated in a dry magnet operating at 7 T. PET and MRI characteristics were assessed complying with international standards and interferences between both subsystems during simultaneous scans were addressed. For the rat size phantom, the peak noise equivalent count rates (NECR) were 96.4 kcps at 30.2 MBq and 132.3 kcps at 28.4 MBq respectively with and without RF coil. For mouse, the peak NECR was 300.0 kcps at 34.5 MBq and 426.9 kcps at 34.3 MBq respectively with and without coil. At the axial centre of the FOV, spatial resolutions expressed as full width at half maximum / full width at tenth maximum (FWHM/FWTM) ranged from 1.69/3.19 mm to 2.39/4.87 mm. The peak absolute sensitivity obtained with a 250-750 keV energy window was 7.5% with coil and 7.9% without coil. Spill over ratios of the NEMA NU4-2008 image quality (NEMA-IQ) phantom ranged from 0.25 to 0.96 and the percentage of non-uniformity was 5.7%. The image count versus activity was linear up to 40 MBq. The principal magnetic field variation was 0.03 ppm/mm over 40 mm. The qualitative and quantitative aspects of data were preserved during simultaneous scans.

Automatic classification of tissues on pelvic MRI based on relaxation times and support vector machine.

Tissue segmentation and classification in MRI is a challenging task due to a lack of signal intensity standardization. MRI signal is dependent on the acquisition protocol, the coil profile, the scanner type, etc. While we can compute quantitative physical tissue properties independent of the hardware and the sequence parameters, it is still difficult to leverage these physical properties to segment and classify pelvic tissues. The proposed method integrates quantitative MRI values (T1 and T2 relaxation times and pure synthetic weighted images) and machine learning (Support Vector Machine (SVM)) to segment and classify tissues in the pelvic region, i.e.: fat, muscle, prostate, bone marrow, bladder, and air. Twenty-two men with a mean age of 30±14 years were included in this prospective study. The images were acquired with a 3 Tesla MRI scanner. An inversion recovery-prepared turbo spin echo sequence was used to obtain T1-weighted images at different inversion times with a TR of 14000 ms. A 32-echo spin echo sequence was used to obtain the T2-weighted images at different echo times with a TR of 5000 ms. T1 and T2 relaxation times, synthetic T1- and T2-weighted images and anatomical probabilistic maps were calculated and used as input features of a SVM for segmenting and classifying tissues within the pelvic region. The mean SVM classification accuracy across subjects was calculated for the different tissues: prostate (94.2%), fat (96.9%), muscle (95.8%), bone marrow (91%) and bladder (82.1%) indicating an excellent classification performance. However, the segmentation and classification for air (within the rectum) may not always be successful (mean SVM accuracy 47.5%) due to the lack of air data in the training and testing sets. Our findings suggest that SVM can reliably segment and classify tissues in the pelvic region.

Automatic deformable PET/MRI registration for preclinical studies based on B-splines and non-linear intensity transformation.

PET images deliver functional data, whereas MRI images provide anatomical information. Merging the complementary information from these two modalities is helpful in oncology. Alignment of PET/MRI images requires the use of multi-modal registration methods. Most of existing PET/MRI registration methods have been developed for humans and few works have been performed for small animal images. We proposed an automatic tool allowing PET/MRI registration for pre-clinical study based on a two-level hierarchical approach. First, we applied a non-linear intensity transformation to the PET volume to enhance. The global deformation is modeled by an affine transformation initialized by a principal component analysis. A free-form deformation based on B-splines is then used to describe local deformations. Normalized mutual information is used as voxel-based similarity measure. To validate our method, CT images acquired simultaneously with the PET on tumor-bearing mice were used. Results showed that the proposed algorithm outperformed affine and deformable registration techniques without PET intensity transformation with an average error of 0.72 ± 0.44 mm. The optimization time was reduced by 23% due to the introduction of robust initialization. In this paper, an automatic deformable PET-MRI registration algorithm for small animals is detailed and validated. Graphical abstract ᅟ.

Bone marrow fat quantification of osteoporotic vertebral compression fractures: comparison of multi-voxel proton MR spectroscopy and chemical-shift gradient-echo MR imaging.

BACKGROUND: Only a few studies have used in/opposed phase method for a quantitative evaluation of fat fraction in the spine. PURPOSE: To compare multivoxel proton MR spectroscopy and chemical-shift gradient-echo MR imaging for bone marrow fat quantification in vertebral compression fractures (VCF). MATERIAL AND METHODS: Vertebral marrow fat quantification in fifteen patients was measured at 3.0-T. Multi-voxel proton spectroscopy (MRS) and in/opposed-phase MR imaging using a fat map build with a triple-echo gradient-echo sequence was used. All the patients had benign vertebral collapse. Bone marrow fat content was evaluated by both techniques in compressed (acute or chronic) and in non-compressed vertebrae. RESULTS: The percentage of fat fraction measured by the triple-echo sequence was well correlated with those calculated by MRS (r(2) = 0.85; P < 10(-4)). There was a significant decrease of fat fraction in acute VCF versus both chronic VCF (P < 10(-9)) and non-fractured vertebrae (P < 10(-7)). There was no significant difference in fat fraction evaluated by both techniques between non-fractured vertebrae and chronic VCF. CONCLUSION: We have validated the in/opposed phase method compared with MRS for vertebral bone marrow fat quantification. The fat mapping using a triple-echo gradient-echo sequence allows distinguishing acute and chronic benign VCF.

Biphasic time course of brain water ADC observed during the first month of life in term neonates with severe perinatal asphyxia is indicative of poor outcome at 3 years.

In severe perinatal asphyxia, the prognostic value of apparent diffusion coefficient (ADC) measurements is still open to question. We hypothesized that temporal and anatomical changes of brain ADC values occurring early after the hypoxic-ischemic insult could predict the outcome at 36 months. To demonstrate this, mean ADC values were calculated for 16 brain structures in 59 term neonates who underwent an MR examination during the first month of life. Neonates were divided into two groups according to their 36-month outcome: unfavorable (death/severe disability) or favorable outcome. ADC values were plotted against age at scan. In neonates with favorable outcomes (n=32), ADC values were constant over the study period. In babies with unfavorable outcomes (n=27), ADCs exhibited two different patterns. In infratentorial structures, ADCs were constant and normal. In supratentorial areas, ADCs followed a biphasic temporal evolution: ADC values were at their lowest at day 2, showed a rapid increase until Days 5-7, and were thereafter similar to those of neonates with favorable outcomes. Using receiver operating characteristic analysis, during the first 3-5 days of life, all neonates with decreased ADC had an unfavorable outcome. These temporal and anatomical changes of ADC values imply that individual prognosis of asphyxiated neonates can only be predicted by measurement of ADC in supratentorial areas within the first 3-5 days of life.

Subcortical gray matter N-acetylaspartate reduction in two cases of vascular dementia.

Many of the previous studies of vascular dementia using proton magnetic resonance (MR) spectroscopy had been carried out on white matter. However, no proton spectroscopic data of the subcortical gray matter are available in such disease. We report two cases suffering from vascular dementia, with an unilateral N-acetylaspartate (NAA) decrease on subcortical gray matter. This significant reduction in NAA ratios was associated with an increase of choline on the ipsilateral centrum semiovale. We discuss the pathophysiology of these cases.

Automatic determination of aortic compliance with cine-magnetic resonance imaging: an application of fuzzy logic theory.

RATIONALE AND OBJECTIVES: Aortic compliance is defined as the relative change in aortic cross-sectional area divided by the change in arterial pressure. Magnetic resonance imaging (MRI) is a useful imaging modality for the noninvasive evaluation of aortic compliance. However, manual tracing of the aortic contour is subject to important interobserver variations. To estimate the aortic compliance from cine-MRI, a method based on fuzzy logic theory was elaborated. MATERIALS AND METHODS: Seven healthy volunteers and eight patients with Marfan syndrome were examined using an ECG gated cine-MRI sequence. The aorta was imaged in the transverse plane at the level of the pulmonary trunk. A method based on fuzzy logic was developed to automatically detect the aortic contour. RESULTS: Through our robust automatic contouring method, the calculation of aortic cross-sectional areas allows an estimation of the aortic compliance. CONCLUSION: The aortic compliance can be obtained from a fuzzy logic based automatic contouring method, thereby avoiding the important interobserver variation often associated with manual tracing.