Stroke without cerebral arteriopathy in sickle cell disease children: causes and treatment.

Cerebral arteriopathy (CA) in children with sickle cell disease (SCD) is classically described as chronic stenosis of arteries in the anterior brain circulation, leading to ischemic stroke. Some studies have however reported strokes in children with SCD but without CA. In order to better understand the etiology and risk factors of these strokes, we retrospectively analyzed ischemic strokes occurring in a large cohort of children over a 13 year-period. Between 2007 and 2020, 25/1500 children with SCD had an ischemic stroke in our center. Among them, 13 (52%) had CA, described as anatomical arterial stenosis, while 12 (48%) did not. Patients with stroke without CA were older than patients with stroke attributed to SCD-CA (9.0 years old vs 3.6 years old, p=0.008), and had more frequently a SC genotype (25% vs 0% respectively). Their stroke involved posterior circulation more frequently, with cerebellar involvement in 42%. Retained stroke etiologies in patients without typical SCD-related CA were reversible cerebral vasoconstriction syndrome, cerebral fat embolism, arterial thrombosis or thromboembolism, hyperviscosity, vasculitis in a context of infectious meningoencephalitis, and severe hemodynamic failure. No recurrence was observed in the 24 months following stroke, even though 67% of the patients were no longer receiving exchange transfusions in this group. In conclusion, in a cohort of pediatric SCD patients with efficient stroke screening strategy, half of occurring ischemic strokes were related to causes other than CA. They affected a different population of SCD children and systematic long-term transfusion programs may not be necessary in these cases.

Juvenile neuropsychiatric systemic lupus erythematosus: A specific clinical phenotype and proposal of a probability score.

OBJECTIVE: Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic auto-immune disease involving several organs. Neuropsychiatric (NP) SLE (NPSLE) is frequent in j-SLE and associated with increased morbidity/mortality. Although NPSLE classification criteria exist, attributing NP features to j-SLE remains a major challenge. The study objective is to thoroughly describe j-NPSLE patients and assist in their diagnosis. METHODS: This is a 4-year retrospective monocentric study of j-SLE patients. NP events were attributed to j-SLE using standardised diagnostic criteria and multidisciplinary paediatric clinical expertise. Clinical features, brain magnetic resonance imaging (MRI)s and samples analysis including cerebrospinal fluid were assessed. A risk of j-NPSLE score was developed based on multivariable logistic regression analysis. RESULTS: Of 39 patients included, 44% were identified as having j-NPSLE. J-NPSLE diagnosis was established at the onset of j-SLE in 59% of patients. In addition to frequent kidney involvement (76%) and chilblains (65%), all j-NPSLE patients displayed psychiatric features: cognitive symptoms (82%), hallucinations (76%), depressed mood (35%), acute confused state (18%) and catatonia (12%). Neurological involvement was often mild and nonspecific, with headache (53%) in about half of the patients. The main features reported on brain MRI were nonspecific T2/FLAIR white matter hyperintensities (65%), and cerebral atrophy (88%). Upon immunosuppressive treatment, clinical improvement of NP features was observed in all j-NPSLE patients. The score developed to attribute j-NPSLE probability, guide further investigations and appropriate treatments is based on hallucinations, memory, sleep and renal involvement (Sensitivity: 0.95 Specificity: 0.85). Cerebrospinal fluid (CSF) neopterin assessment increases the score sensitivity and specificity. CONCLUSION: Physicians should carefully and systematically assess the presence of NP features at diagnosis and early stages of j-SLE. For j-NPSLE patients with predominant psychiatric features, a multidisciplinary collaboration, including psychiatrists, is essential for the diagnosis, management and follow-up.

Juvenile Neuropsychiatric Systemic Lupus Erythematosus: Identification of Novel Central Neuroinflammation Biomarkers.

INTRODUCTION: Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic autoimmune disease affecting multiple organs. Ranging from minor features, such as headache or mild cognitive impairment, to serious and life-threatening presentations, j-neuropsychiatric SLE (j-NPSLE) is a therapeutic challenge. Thus, the diagnosis of NPSLE remains difficult, especially in pediatrics, with no specific biomarker of the disease yet validated. OBJECTIVES: To identify central nervous system (CNS) disease biomarkers of j-NPSLE. METHODS: A 5-year retrospective tertiary reference monocentric j-SLE study. A combination of standardized diagnostic criteria and multidisciplinary pediatric clinical expertise was combined to attribute NP involvement in the context of j-SLE. Neopterin and interferon-alpha (IFN-α) protein levels in cerebrospinal fluid (CSF) were assessed, together with routine biological and radiological investigations. RESULTS: Among 51 patients with j-SLE included, 39% presented with j-NPSLE. J-NPSLE was diagnosed at onset of j-SLE in 65% of patients. No specific routine biological or radiological marker of j-NPSLE was identified. However, CSF neopterin levels were significantly higher in active j-NPSLE with CNS involvement than in j-SLE alone (p = 0.0008). Neopterin and IFN-α protein levels in CSF were significantly higher at diagnosis of j-NPSLE with CNS involvement than after resolution of NP features (respectively p = 0.0015 and p = 0.0010) upon immunosuppressive treatment in all patients tested (n = 10). Both biomarkers correlated strongly with each other (Rs = 0.832, p < 0.0001, n = 23 paired samples). CONCLUSION: CSF IFN-α and neopterin constitute promising biomarkers useful in the diagnosis and monitoring of activity in j-NPSLE.

Enhancing fetal alcohol spectrum disorders diagnosis with a classifier based on the intracerebellar gradient of volumetric undersizing.

In fetal alcohol spectrum disorders (FASD), brain growth deficiency is a hallmark of subjects both with fetal alcohol syndrome (FAS) and with non-syndromic FASD (NS-FASD, i.e., those without specific diagnostic features). However, although the cerebellum was suggested to be more severely undersized than the rest of the brain, it has not yet been given a specific place in the FASD diagnostic criteria where neuroanatomical features still count for little if anything in diagnostic specificity. We applied a combination of cerebellar segmentation tools on a 1.5 T 3DT1 brain MRI dataset from a monocentric population of 89 FASD (52 FAS, 37 NS-FASD) and 126 typically developing controls (6-20 years old), providing 8 volumes: cerebellum, vermis and 3 lobes (anterior, posterior, inferior), plus total brain volume. After adjustment of confounders, the allometric scaling relationship between these cerebellar volumes (Vi ) and the total brain or cerebellum volume (Vt ) was fitted (Vi = bVt a ), and the effect of group (FAS, control) on allometric scaling was evaluated. We then estimated for each cerebellar volume in the FAS population the deviation from the typical scaling (v DTS) learned in the controls. Lastly, we trained and tested two classifiers to discriminate FAS from controls, one based on the total cerebellum v DTS only, the other based on all the cerebellar v DTS, comparing their performance both in the FAS and the NS-FASD group. Allometric scaling was significantly different between FAS and control group for all the cerebellar volumes (p < .001). We confirmed the excess of total cerebellum volume deficit (v DTS = -10.6%) and revealed an antero-inferior-posterior gradient of volumetric undersizing in the hemispheres (-12.4%, 1.1%, 2.0%, respectively) and the vermis (-16.7%, -9.2%, -8.6%, repectively). The classifier based on the intracerebellar gradient of v DTS performed more efficiently than the one based on total cerebellum v DTS only (AUC = 92% vs. 82%, p = .001). Setting a high probability threshold for >95% specificity of the classifiers, the gradient-based classifier identified 35% of the NS-FASD to have a FAS cerebellar phenotype, compared to 11% with the cerebellum-only classifier (pFISHER = 0.027). In a large series of FASD, this study details the volumetric undersizing within the cerebellum at the lobar and vermian level using allometric scaling, revealing an anterior-inferior-posterior gradient of vulnerability to prenatal alcohol exposure. It also strongly suggests that this intracerebellar gradient of volumetric undersizing may be a reliable neuroanatomical signature of FAS that could be used to improve the specificity of the diagnosis of NS-FASD.

Combining neuroanatomical features to support diagnosis of fetal alcohol spectrum disorders.

AIM: To identify easily accessible neuroanatomical abnormalities useful for diagnosing fetal alcohol spectrum disorders (FASD) in fetal alcohol syndrome (FAS) but more importantly for the probabilistic diagnosis of non-syndromic forms (NS-FASD). METHOD: We retrospectively collected monocentric data from 52 individuals with FAS, 37 with NS-FASD, and 94 paired typically developing individuals (6-20 years, 99 males, 84 females). On brain T1-weighted magnetic resonance imaging, we measured brain size, corpus callosum length and thicknesses, vermis height, then evaluated vermis foliation (Likert scale). For each parameter, we established variations with age and brain size in comparison individuals (growth and scaling charts), then identified participants with abnormal measurements (<10th centile). RESULTS: According to growth charts, there was an excess of FAS with abnormally small brain, isthmus, splenium, and vermis. According to scaling charts, this excess remained only for isthmus thickness and vermis height. The vermis foliation was pathological in 18% of those with FASD but in no comparison individual. Overall, 39% of those with FAS, 27% with NS-FASD, but only 2% of comparison individuals presented with two FAS-recurrent abnormalities, and 19% of those with FAS had all three. Considering the number of anomalies, there was a higher likelihood of a causal link with alcohol in 14% of those with NS-FASD. INTERPRETATION: Our results suggest that adding an explicit composite neuroanatomical-radiological criterion for FASD diagnosis may improve its specificity, especially in NS-FASD. WHAT THIS PAPER ADDS: Neuroanatomical anomalies independent of microcephaly can be measured with clinical-imaging tools. Small-for-age brain, small-for-brain-size callosal isthmus or vermian height, and disrupted vermis foliation are fetal alcohol syndrome (FAS)-recurrent anomalies. Associations of these anomalies are frequent in fetal alcohol spectrum disorder (FASD) even without FAS, while exceptional in typically developing individuals. These associations support higher likelihood of causal link with alcohol in some individuals with non-syndromic FASD. A new explicit and composite neuroanatomical-radiological criterion can improve the specificity of FASD diagnosis.

Evolution of Extracranial Internal Carotid Artery Disease in Children With Sickle Cell Anemia.

BACKGROUND: Cerebral arteriopathy in patients with sickle cell anemia mainly affects the intracranial anterior circulation. However, the extracranial internal carotid artery (eICA) can also be stenosed and responsible for ischemic lesions. In children with sickle cell anemia, we perform routine annual Doppler ultrasound assessment of the eICA and magnetic resonance imaging with 3-dimensional time-of-flight magnetic resonance angiography of the Willis circle and neck arteries in those with abnormal velocity. Our aim was to report the evolution of eICA stenoses from 2011 to the present as a function of therapy in a retrospective case-series study. We hypothesized that chronic transfusion (CTT) would be more effective than hydroxyurea and simple observation on the evolution of eICA stenosis. METHODS: Eligibility criteria were a history of eICA velocity ≥160 cm/s with a minimum Doppler and magnetic resonance imaging follow-up of 1 year. eICAs were graded for stenosis according to NASCET (The North American Symptomatic Carotid Endarterectomy Trial). Magnetic resonance imaging was investigated for ischemic lesions. Treatment with hydroxyurea and CTT were obtained from the chart review. RESULTS: Fifty-four patients were included. Eight patients had a stroke history. The median (range) follow-up was 4.7 years (1.1-9.2 years). On the first neck magnetic resonance angiography, stenosis was present in 48/54 (89%) patients. Kinking was found in 39/54 (72%) patients. On the last neck magnetic resonance angiography, the proportion of patients with eICA stenosis decreased to 39/54 (72%). ICA occlusion occurred in 5 patients despite CTT. Three patients had carotid webs without intracranial stenosis. The proportion of patients with improvement in stenosis score was 8% with no treatment intensification, 20% with hydroxyurea, and 48% with CTT (P=0.016). The mean (SD) change per year in stenosis score was 0.40 (0.60) without intensification, 0.20 (0.53) with hydroxyurea, and -0.18 (0.55) with CTT (P=0.006). Ischemic lesions were present initially in 46% of patients, and the incidence of progressive ischemic lesions was 2.5 events/100 patient-years. Cox regression analysis showed that the initial score for eICA stenosis was a significant predictive factor for the risk of new silent cerebral infarct events. CONCLUSIONS: Our study reinforces the need to assess cervical arteries for better prevention of cerebral ischemia and encourage initiation of CTT in sickle cell anemia children with eICA stenosis.

In vivo biochemical investigation of spermatogenic status: 1H-MR spectroscopy of testes with nonobstructive azoospermia.

OBJECTIVES: To evaluate the biochemical milieu in testes with nonobstructive azoospermia (NOA) by using proton MR spectroscopy (1H-MRS) in detecting differences in testicular metabolites between histological stages of NOA and in assessing the possible presence of spermatozoa before microdissection testicular sperm extraction (mTESE). METHODS: Forty-nine NOA men and fifty age-matched controls were included in this prospective study. A single-voxel point-resolved spectroscopy sequence with TR/TE (2000/25 ms) was used. NOA testes were classified using the higher Johnsen score (hJS) (group 1, hJS ≥ 8; and group 2, hJS < 8). Nonparametric statistical tests were used to assess differences in normalized metabolite concentrations, defined as ratios of the metabolite concentrations versus creatine concentration between (a) NOA and controls, (b) NOA groups, and (c) NOA with positive and negative sperm retrieval. RESULTS: Normalized concentrations of total choline (median 0.396 vs 1.09 mmol/kg, p = 0.002), myo-inositol (median 1.985 vs 3.19 mmol/kg, p = 0.002), and total lipids and macromolecules (TLM) resonating at 0.9 ppm (median 0.962 vs 2.43 mmol/kg, p = 0.024), 1.3 ppm (median 4.88 vs 10.7 mmol/kg, p = 0.043), and 2.0 ppm (median 2.33 vs 5.96 mmol/kg, p = 0.007) were reduced in NOA testes compared with controls. Decreased concentrations of TLM 2.0 (median 3.755 vs 0.436 mmol/kg, p = 0.043) were found in group 2 compared with group 1. Increased normalized concentrations of glutamate were observed in NOA testes with failed sperm retrieval (median 0.321 vs 0.000 mmol/kg, p = 0.028). CONCLUSIONS: 1H-MRS provides metabolic information about the testis in NOA patients and assesses spermatogenic status before mTESE. KEY POINTS: • NOA testes differed from age-matched controls, in terms of reduced normalized concentrations of tChol, mI, and lipids. • TLM 2.0 peaks were found useful in the identification of NOA testes with the presence of foci of advanced spermatogenesis up to the haploid gamete stage. • Glu proved a reliable metabolic signature of spermatogenesis in NOA population by assessing the possible presence of sperm after mTESE.

Testicular Apparent Diffusion Coefficient and Magnetization Transfer Ratio: Can These MRI Parameters Be Used to Predict Successful Sperm Retrieval in Nonobstructive Azoospermia?

OBJECTIVE. The aim of our study was to assess if testicular apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR) can be used as MRI parameters to predict the presence of spermatozoa retrieved after microdissection testicular sperm extraction (mTESE) in men with nonobstructive azoospermia (NOA). MATERIALS AND METHODS. The study included 49 men with NOA and 45 age-matched control subjects. Participants underwent scrotal MRI between June 2013 and January 2017, 1 day before mTESE. Testicular volume (TV), ADC, and MTR were measured. NOA testes were classified as follows: group 1, testes with higher Johnsen score of ≥ 8; and group 2, testes with higher Johnsen score of < 8. Nonparametric statistical tests were used to assess differences in TV, ADC, and MTR between men with NOA and control subjects, the two NOA groups, and NOA testes with positive sperm retrieval and NOA testes with negative sperm retrieval. RESULTS. TV (p < 0.001) was reduced and both ADC (p < 0.001) and MTR (p = 0.013) were increased in NOA testes compared with normal testes. A positive correlation between higher Johnsen score and TV (p < 0.001) and a negative correlation between higher Johnsen score and both ADC (p = 0.015) and MTR (p = 0.003) were found. TV (p < 0.001) was reduced in NOA testes with failed sperm retrieval compared with NOA testes with positive sperm retrieval. On the contrary, ADC (p = 0.011) and MTR (p = 0.045) were significantly increased in NOA testes with negative sperm retrieval. CONCLUSION. On the basis of our preliminary data, TV, ADC, and MTR might represent useful MRI parameters in the workup of patients with NOA by helping to predict the presence of spermatozoa after mTESE.

Diffusion tensor imaging as an adjunct tool for the diagnosis of varicocele.

A noninvasive imaging technique providing information about testicular dysfunction in testes with varicocele would be useful. The aim is to measure the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in testes of infertile men with varicocele and to assess interobserver agreement. Sixteen infertile men with varicocele and 14 age-matched controls underwent 1.5 T diffusion tensor imaging (DTI) MRI. Testicular ADC and FA were measured by two radiologists independently. Parametric and nonparametric statistical tests were applied to compare between the ADC and FA of testes with varicocele and normal testes. Interobserver agreement was evaluated. The interobserver variability for ADC (0.915) and FA (0.948) was very good. No differences in ADC (p = 0.294) were found between the two groups. FA was significantly lower in testes with varicocele compared to age-matched controls (p < 0.001). An optimal cut-off of FA 0.08 was found for the diagnosis of varicocele (sensitivity = 88%, specificity = 93.5%, positive predictive value = 91.6% and negative predictive value = 90.6%). Based on our results, FA is useful for the diagnosis of testes in infertile men with varicocele, with very good interobserver agreement. Therefore, DTI may be used as a noninvasive imaging tool in the work-up of varicocele.

Diffusion tensor imaging parameters in testes with nonobstructive azoospermia.

BACKGROUND: The development of noninvasive imaging parameters having the capacity to identify the population of men with nonobstructive azoospermia (NOA) where a successful sperm retrieval outcome is of great clinical significance. PURPOSE/HYPOTHESIS: To assess differences of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in NOA testes with impaired spermatogenesis and the possible association with the presence of spermatozoa after testicular sperm extraction (TESE). STUDY TYPE: Retrospective. POPULATION: Twenty NOA men (35 testes) and 21 age-matched controls (36 testes). FIELD STRENGTH/SEQUENCE: 1.5T, T1 WI-SE T2 WI-FSE FS SS-EP-DTI. ASSESSMENTS: The MRI data were analyzed by two radiologists in consensus. The average ADC and FA of testicular parenchyma was measured. NOA testes were classified as NOA with higher Johnsen score (JS) ≥8 (group 1) and JS <8 (group 2). STATISTICAL TESTS: Parametric and nonparametric statistical tests were used to compare ADC and FA between NOA groups and normal testes (group 3) and to evaluate a possible association with the presence of spermatozoa after TESE. RESULTS: Differences in ADC were found between groups 1 and 2 (P = 0.043) and groups 2 and 3 (P = 0.004), but not between groups 1 and 3 (P = 0.418). Higher values of FA were found both in NOA testes with JS ≥8 (P < 0.001) and JS <8 (P < 0.001) compared to controls. ADC (P = 0.096) and FA (P = 0.516) did not demonstrate differences in NOA testes with or without spermatozoa at TESE. DATA CONCLUSION: Both ADC and FA are increased in NOA testes compared to a normal population. ADC was proven to be a more useful diagnostic adjunct tool in the identification of the population of NOA men with foci of advanced spermatogenesis. However, DTI parameters were not predictive of sperm retrieval after TESE. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1318-1325.

MRI of the scrotum: Recommendations of the ESUR Scrotal and Penile Imaging Working Group.

OBJECTIVES: The Scrotal and Penile Imaging Working Group (SPI-WG) appointed by the board of the European Society of Urogenital Radiology (ESUR) has produced recommendations for magnetic resonance imaging (MRI) of the scrotum. METHODS: The SPI-WG searched for original and review articles published before September 2016 using the Pubmed and Medline databases. Keywords used were 'magnetic resonance imaging', 'testis or testicle or testicular', 'scrotum', 'intratesticular', 'paratesticular', 'extratesticular' 'diffusion-weighted', 'dynamic MRI'. Consensus was obtained among the members of the subcommittee. The expert panel proposed recommendations using Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence. RESULTS: The recommended MRI protocol should include T1-, T2-weighted imaging, diffusion-weighted imaging and dynamic contrast-enhanced MRI. Scrotal MRI can be clinically applied for lesion characterisation (primary), including both intratesticular and paratesticular masses, differentiation between germ-cell and non-germ-cell neoplasms (evolving), characterisation of the histological type of testicular germ cell neoplasms (TGCNs, in selected cases), local staging of TGCNs (primary), acute scrotum (in selected cases), trauma (in selected cases) and undescended testes (primary). CONCLUSIONS: The ESUR SPI-WG produced this consensus paper in which the existing literature on MRI of the scrotum is reviewed. The recommendations for the optimal imaging technique and clinical indications are presented. KEY POINTS: • This report presents recommendations for magnetic resonance imaging (MRI) of the scrotum. • Imaging acquisition protocols and clinical indications are provided. • MRI is becoming established as a worthwhile second-line diagnostic tool for scrotal pathology.

Normal testes asymmetry evaluated by apparent diffusion coefficient and magnetization transfer ratio.

Background In humans, the left testis generally hangs lower than the right and the right is larger than the left. Magnetic resonance imaging (MRI) represents an important adjuvant modality in the investigation of testicular diseases. Purpose To assess if normal testes asymmetry is related to apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR). Material and Methods The normal testes from 106 men were included. Testicular volume (TV) was calculated by using the ellipsoid formula: length × width × height × 0.52. Diffusion-weighted imaging was performed using a SS EPI diffusion pulse sequence and b-values of 0 and 900 s/mm-2. Magnetization transfer imaging was obtained using a 3D GRE sequence both with and without an off-resonance radiofrequency pulse. MTR maps were obtained by the following formula: (SIo-SIm) / (SIo) × 100%, where SIo and SIm represent the signal intensity in the baseline image and that in the corresponding image acquired with an off-resonance MT pulse, respectively. The mean and standard deviation of testicular volume (TV), ADC, and MTR of both testes was calculated and compared using a paired sample t-test. Results The mean TV (mL) was greater ( P = 0.006) for the right testis (16.77 ± 4.84) compared to the left (15.97 ± 4.45). ADC of the right testis (1.09 ± 0.12 × 10 - 3 mm2 s-1) was not different ( P = 0.064) from that of the left testis (1.07 ± 0.12 × 10-3 mm2 s-1). Differences ( P = 0.032) were observed between MTR of the right (46.6 ± 2.1%) and left testis (46.0 ± 2.2%). Conclusion The reported differences in paired testes size was confirmed, introducing a possible relationship with structural and functional asymmetry of normal testes, based on MTR.

MR Spectra of Normal Adult Testes and Variations with Age: Preliminary Observations.

OBJECTIVES: The aim was to determine the proton MR (1H-MR) spectra of normal adult testes and variations with age. METHODS: Forty-one MR spectra of normal testes, including 16 testes from men aged 20-39 years (group I) and 25 testes from men aged 40-69 years (group II), were analyzed. A single-voxel point-resolved spectroscopy sequence (PRESS), with TR/TE: 2000/25 ms was used. The volume of interest was placed to include the majority of normal testicular parenchyma. Association between normalized metabolite concentrations, defined as ratios of the calculated metabolite concentrations relative to creatine concentration, and age was assessed. RESULTS: Quantified metabolites of the spectra were choline (Cho), creatine (Cr), myo-inositol (mI), scyllo-inositol, taurine, lactate, GLx compound, glucose, lipids, and macromolecules resonating at 0.9 ppm (LM09), around 20 ppm (LM20), and at 13 ppm (LM13). Most prominent peaks were Cho, Cr, mI, and lipids. A weak negative correlation between mI and age (P = 0.015) was observed. Higher normalized concentrations of Cho (P = 0.03), mI (P = 0.08), and LM13 (P = 0.05) were found in group I than in group II. CONCLUSIONS: 1H-MR spectra of a normal adult testis showed several metabolite peaks. A decrease of levels of Cho, mI, and LM13 was observed with advancing age. KEY POINTS: • Single-voxel PRESS MRS of a normal testis is feasible. • 1H-MR spectra of a normal testis showed several metabolite peaks. • Most prominent peaks were Cho, Cr, mI, and lipids. • A decrease of Cho, mI, and LM13 was seen with advancing age.

Magnetization transfer imaging of normal and abnormal testis: preliminary results.

OBJECTIVES: The aim was to determine the magnetization transfer ratio (MTR) of normal testes, possible variations with age and to assess the feasibility of MTR in characterizing various testicular lesions. METHODS: Eighty-six men were included. A three-dimensional gradient-echo MT sequence was performed, with/without an on-resonance binomial prepulse. MTR was calculated as: (SIo-SIm)/(SIo) × 100 %, where SIm and SIo refers to signal intensities with and without the saturation pulse, respectively. Subjects were classified as: group 1, 20-39 years; group 2, 40-65 years; and group 3, older than 65 years of age. Analysis of variance (ANOVA) followed by the least significant difference test was used to assess variations of MTR with age. Comparison between the MTR of normal testis, malignant and benign testicular lesions was performed using independent-samples t testing. RESULTS: ANOVA revealed differences of MTR between age groups (F = 7.51, P = 0.001). Significant differences between groups 1, 2 (P = 0.011) and 1, 3 (P < 0.001) were found, but not between 2, 3 (P = 0.082). The MTR (in percent) of testicular carcinomas was 55.0 ± 3.2, significantly higher than that of benign lesions (50.3 ± 4.0, P = 0.02) and of normal testes (47.4 ± 2.2, P < 0.001). CONCLUSIONS: MTR of normal testes decreases with age. MTR might be helpful in the diagnostic work-up of testicular lesions. KEY POINTS: MTR of normal testes shows age-related changes. Testicular carcinomas have high MTR values. MTR may be useful in the diagnostic work-up of testicular lesions.

Brain 18 F-FDG PET reveals cortico-subcortical hypermetabolic dysfunction in juvenile neuropsychiatric systemic lupus erythematosus.

BACKGROUND: In juvenile systemic lupus erythematosus (j-SLE) with neuropsychiatric (NP) symptoms, there is a lack of diagnostic biomarkers. Thus, we study whether PET-FDG may identify any metabolic dysfunction in j-NPSLE. METHODS: A total of 19 18FDG-PET exams were consecutively performed using PET-MRI system in 11 non-sedated patients presenting with j-NPSLE (11-18y) for less than 18 months (m) and without any significant lesion at MRI. Psychiatric symptoms were scored from 0 (none) to 3 (severe) at PET time. PET images were visually analyzed and voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping (spm) with an age-matched control group, at threshold set > 50 voxels using both p < 0.001 uncorrected (unc.) and p < 0.05 corrected family wise error (FWE). RESULTS: Patients exhibited mainly psychiatric symptoms, with diffuse inflammatory j-NPSLE. First PET (n = 11) was performed at a mean of 15y of age, second/third PET (n = 7/n = 1) 6 to 19 m later. PET individual analysis detected focal bilateral anomalies in 13/19 exams visually but 19/19 using spm (unc.), mostly hypermetabolic areas (18/19). A total of 15% of hypermetabolic areas identified by spm had been missed visually. PET group analysis (n = 19) did not identify any hypometabolic area, but a large bilateral cortico-subcortical hypermetabolic pattern including, by statistical decreasing order (unc.), thalamus, subthalamic brainstem, cerebellum (vermis and cortex), basal ganglia, visual, temporal and frontal cortices. Mostly the subcortical hypermetabolism survived to FWE analysis, being most intense and extensive (51% of total volume) in thalamus and subthalamus brainstem. Hypermetabolism was strictly subcortical in the most severe NP subgroup (n = 8, scores 2-3) whereas it also extended to cerebral cortex, mostly visual, in the less severe subgroup (n = 11, scores 0-1), but difference was not significant. Longitudinal visual analysis was inconclusive due to clinical heterogeneity. CONCLUSIONS: j-NPSLE patients showed a robust bilateral cortico-subcortical hypermetabolic network, focused subcortically, particularly in thalamus, proportionally to psychiatric features severity. Further studies with larger, but homogeneous, cohorts are needed to determine the sensitivity and specificity of this dysfunctional pattern as a potential biomarker in diffuse inflammatory j-NPSLE with normal brain MRI.

A preliminary study of the biochemical environment of infertile testes with clinical varicocele.

PURPOSE: To investigate the role of proton magnetic resonance spectroscopy. (1H-MRS) in the assessment of the biochemical environment of testes in infertile men with clinical varicocele. METHODS: In this prospective IRB approved study, 13 infertile men with clinical varicocele and 11 age-matched controls were assessed. 1H-MRS was performed using a single voxel point-resolved spectroscopy (PRESS) sequence with TR/TE: 2000/25 ms. Normalized metabolite concentrations, defined as ratios of the calculated metabolite concentrations relative to total creatine (tCr) concentration were compared between infertile testes with clinical varicocele and normal testes using nonparametric statistical tests. Logistic regression analysis was performed to assess the most significant predictor for the diagnosis of varicocele. RESULTS: Several metabolic peaks were found in both infertile testes with clinical varicocele and normal testes. Most prominent peaks were the following: total choline (tCho), tCr, myo-inositol (mI), Glx, and total lipids and macromolecules resonating at 0.9 ppm (TLM09), 1.3 ppm (TLM13) and 2.0 ppm (TLM20). Lower normalized concentrations of tCho (P = 0.001), mI (P = 0.012), Glx (P = 0.011), TLM09 (P = 0.027), TLM13 (P = 0.035) and TLM20 (P = 0.021) were found in infertile testes with clinical varicocele compared with normal men. Total Cho proved the most significant predictor for the diagnosis of clinical varicocele (P = 0.001). CONCLUSIONS: 1H-MR spectra of infertile testes with clinical varicocele showed decrease in normalized concentrations of tChol, ml, Glx and lipids. 1H-MRS of the testes might be used as a noninvasive marker of deranged spermatogenesis in infertile men with clinical varicocele.

Sonographically indeterminate scrotal masses: how MRI helps in characterization.

Magnetic resonance imaging (MRI) of the scrotum represents a useful supplemental imaging technique in the characterization of scrotal masses, particularly recommended in cases of nondiagnostic ultrasonographic findings. An accurate characterization of the benign nature of scrotal masses, including both intratesticular and paratesticular ones may improve patient management and decrease the number of unnecessary radical surgical procedures. Alternative treatment strategies, including follow-up, lesion biopsy, tumor enucleation, or organ sparing surgery may be recommended. The aim of this pictorial review is to present how MRI helps in the characterization of sonographically indeterminate scrotal masses and to emphasize the key MRI features of benign scrotal masses.