Assessment of 3-T MRI using susceptibility-weighted imaging to detect and evaluate intra- or periarticular blood metabolites and meniscal tears of the knee

Purpose: The purpose of this study was to assess the suitability of susceptibility-weighted imaging (SWI) sequences using the 3T MRI-unit for assessment of potential intraarticular pathologies in patients with acute and chronic torsion trauma of the knee joint. Material and methods: Sixty-three patients with subacute and chronic rotary knee joint trauma of either the left or right knee were studied using an Achieva MRI 3T device (Philips, Amsterdam, Netherlands). Ground truth was set by two expert radiologists with seven and 10 years of experience in musculoskeletal imaging. Readings were performed separately for meniscus and joint space including synovia, ligaments, and periarticular soft tissue. Haemorrhage was defined as any lesion that was either T1 or SWI positive, without proton density (PD)-hypointensity (calcification). A lesion was defined as any pathology/variant with any signal positivity of either T1, PD, or SWI. Results: A total of 63 patients were included (F : M = 22 : 41). The median age of the cohort was 29 years (range 13 to 71 years). Thirty-nine patients showed a meniscal tear, and only three of them (7.7%) demonstrated a meniscal haemorrhage. A total of 18 patients suffered from a periarticular injury, and 16 patients (88.9%) demonstrated a concomitant periarticular haemorrhage. Conclusions: These data suggest that SWI can be used for the diagnosis of intra- or periarticular blood metabolites because their potential have an impact on mechanical conflict with the surface of the knee joints, in particular the cartilage and their effect on malacic lesions, but it performs poorly in the detection of meniscal pathologies

Correlation of Patellofemoral Chondromalacia and Body Mass Index (BMI) in Relation to Sex and Age Analysis of 1.5T and 3.0T Magnetic Resonance (MR) Images Using the Outerbridge Scale.

BACKGROUND Cartilage disease (chondromalacia) is most commonly found in the patellofemoral joint. Non-invasive magnetic resonance imaging methods are used to assess the severity of chondromalacia. The available literature lacks papers describing the predilection of chondromalacia changes to BMI assessed on the basis of geometric data that can be assessed by 1.5T and 3.0T MRI. The aim of this study was to assess the relationship between the severity of chondromalacia of the patellofemoral joint and age, sex, and BMI assessed on the 1.5T and 3.0T MRI scanners. MATERIAL AND METHODS The study involved 324 patients, including 159 (49%) women and 165 (51%) men, aged 8-87 years (mean age: 45.1±20.9). The studied group had a BMI in the range of 14.3-47.3 (M: 27.7±5.02). A 1.5T and 3.0T MRI scanner were used in the study. To assess the cartilage of the patellofemoral joint, Outerbridge scales were used. RESULTS The age of the patients showed a significant correlation (Spearman's rank, P0.05).  Significant more degeneration was found at the 1.5T scanner compared to the 3.0T MRI (P<0.0025). CONCLUSIONS The severity of chondromalacia significantly depends on age and BMI level. There is a stronger correlation between the degree of chondromalacia and BMI in women than in men

Relationship between Outerbridge Scale and Chondropathy Femorotibial Joint in Relation to Gender and Age-The Use of 1.5T and 3.0T MRI Scanners.

Background and Objective: Magnetic resonance imaging (MRI) enables the effective evaluation of chondromalacia of the knee joint. Cartilage disease is affected by many factors, including gender, age, and body mass index (BMI). The aim of this study was to check the relationship between the severity of chondromalacia of the femoro-tibial joint and age, gender, and BMI assessed with 1.5T and 3.0T MRI scanners. Materials and Methods: The cross-observational study included 324 patients-159 (49%) females and 165 (51%) males aged 8-87 (45.1 ± 20.9). The BMI of study group was between 14.3 and 47.3 (27.7 ± 5.02). 1.5T and 3.0T MRI scanners were used in the study. The articular cartilage of the knee joint was assessed using the Outerbridge scale. Results: The age of the patients showed a significant correlation with Outerbrige for each compartment of the femorotibial joint (Spearman's rank correlation rho: 0.69-0.74, p &lt; 0.0001). A higher correlation between BMI and Outerbridge was noted in the femur medial (rho = 0.45, p &lt; 0.001) and the tibia medial (rho = 0.43, p &lt; 0.001) than in the femur lateral (rho = 0.29, p &lt; 0.001) and the tibia lateral compartment (rho = 0.34, p &lt; 0.001). Conclusions: The severity of chondromalacia significantly depends on age and BMI level, regardless of gender

Knee Diameter and Cross-Section Area Measurements in MRI as New Promising Methods of Chondromalacia Diagnosis-Pilot Study.

Background and Objectives: Chondromalacia often affects the knee joint. Risk factors for the development of cartilage degenerative changes include overweight, female sex and age. The use of radiological parameters to assess the knee joint is rarely reported in the literature. Materials and Methods: The study involved 324 patients, including 159 (49%) women and 165 (51%) men, with an age range between 8-87 years (mean: 45.1 ± 20.9). The studied group had a body mass index (BMI) in the range of 14.3-47.3 (mean: 27.7 ± 5.02). A 1.5 Tesla and 3.0 Tesla (T) MRI scanner was used to assess the cartilage of the knee joint using the Outerbridge scale. The radiological parameters analyzed were the Insall-Salvati index, knee surface area, knee AP (antero-posterior) maximal diameter and knee SD (sinistro-dexter) maximal diameter. Results: Parameters such as the knee surface area, knee AP maximal diameter and knee SD maximal diameter showed a significant correlation with Outerbridge Scale (p &lt; 0.014). The age of the patients showed a significant correlation with each knee parameter (p &lt; 0.004). Results of knee AP and SD maximal diameter measurements strongly depended on BMI level. Conclusions: A significant relationship was found between the knee surface area, knee AP maximal diameter and knee SD maximal diameter and the advancement of chondromalacic changes in the knee joint, age and BMI

The endolysosomal adaptor PLEKHM1 is a direct target for both mTOR and MAPK pathways

The lysosome is a cellular signalling hub at the point of convergence of endocytic and autophagic pathways, where the contents are degraded and recycled. Pleckstrin homology domain-containing family member 1 (PLEKHM1) acts as an adaptor to facilitate the fusion of endocytic and autophagic vesicles with the lysosome. However, it is unclear how PLEKHM1 function at the lysosome is controlled. Herein, we show that PLEKHM1 co-precipitates with, and is directly phosphorylated by, mTOR. Using a phospho-specific antibody against Ser432/S435 of PLEKHM1, we show that the same motif is a direct target for ERK2-mediated phosphorylation in a growth factor-dependent manner. This dual regulation of PLEKHM1 at a highly conserved region points to a convergence of both growth factor- and amino acid-sensing pathways, placing PLEKHM1 at a critical juncture of cellular metabolism

Evaluation of Transperineal Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy Compared to Transrectal Systematic Biopsy in the Prediction of Tumour Aggressiveness in Patients with Previously Negative Biopsy

Objectives: We compared the transperineal MRI/ultrasoundfusion biopsy (fusPbx) to transrectal systematic biopsy (sys-Pbx) in patients with previously negative biopsy and investigated the prediction of tumour aggressiveness with regard to radical prostatectomy (RP) specimen. Material and Methods: A total of 710 patients underwent multiparametric magnetic resonance imaging (mpMRI), which was evaluated in accordance with Prostate Imaging Reporting and Data System (PI-RADS). The maximum PI-RADS (maxPI-RADS) was defined as the highest PI-RADS of all lesions detected in mpMRI. In case of proven prostate cancer (PCa) and performed RP, tumour grading of the biopsy specimen was compared to that of the RP. Significant PCa (csPCa) was defined according to Epstein criteria. Results: Overall, scPCa was detected in 40% of patients. The detection rate of scPCa was 33% for fusPbx and 25% for sysPbx alone (p < 0.005). Patients with a maxPI-RADS ≥3 and a prostate specific antigen (PSA)-density ≥0.2 ng/mL2 harboured more csPCa than those with a PSA-density < 0.2 ng/mL2 (41% [33/81] vs. 20% [48/248]; p < 0.001). Compared to the RP specimen (n = 140), the concordance of tumour grading was 48% (γ = 0.57), 36% (γ = 0.31) and 54% (γ = 0.6) in fusPbx, sysPbx and comPbx, respectively. Conclusions: The combination of fusPbx and sysPbx outperforms both biopsy modalities in patients with re-biopsy. Additionally, the PSA-density may represent a predictor for csPCa in patients with maxPI-RADS ≥3

Serum miRNAs Support the Indication for MRI-Ultrasound Fusion-Guided Biopsy of the Prostate in Patients with Low-PI-RADS Lesions

Multiparametric MRI (mpMRI) and targeted biopsy of the prostate enhance the tumor detection rate. However, the prediction of clinically significant prostate cancer (PCa) is still limited. Our study tested the additional value of serum levels of selected miRNAs in combination with clinical and mpMRI information for PCa prediction and classification. A total of 289 patients underwent targeted mpMRI-ultrasound fusion-guided prostate biopsy complemented by systematic biopsy. Serum miRNA levels of miRNAs (miR-141, miR-375, miR-21-5p, miR-320b, miR-210-3p, let-7c, and miR-486) were determined by quantitative PCR. Detection of any PCa and of significant PCa were the outcome variables. The patient age, pre-biopsy PSA level, previous biopsy procedure, PI-RADS score, and serum miRNA levels were covariates for regularized binary logistic regression models. The addition of miRNA expression of miR-486 and let-7c to the baseline model, containing only clinical parameters, increased the predictive accuracy. Particularly in patients with PI-RADS ≤3, we determined a sensitivity for detecting significant PCa (Gleason score ≥ 7a corresponding to Grade group ≥2) of 95.2%, and an NPV for absence of significant PCa of 97.1%. This accuracy could be useful to support patient counseling in selected cases

The Function of Hypoxia-Inducible Factor (HIF) Is Independent of the Endoplasmic Reticulum Protein OS-9

The protein “amplified in osteosarcoma-9” (OS-9) has been shown previously to interact with the prolyl hydroxylases PHD2 and PHD3. These enzymes initiate oxygen-dependent degradation of the α-subunit of hypoxia-inducible factor (HIF), a transcription factor that adapts cells to insufficient oxygen supply (hypoxia). A new model has been proposed where OS-9 triggers PHD dependent degradation of HIF-α. It was the aim of our study to define the molecular mode of action of OS-9 in the regulation of PHD and HIF activity. Although initial co-immunoprecipitation experiments confirmed physical interaction between OS-9 and PHD2, neither overexpression nor lentiviral inhibition of OS-9 expression affected HIF regulation. Subcellular localization experiments revealed a distinct reticular staining pattern for OS-9 while PHD2 was mainly localized in the cytoplasm. Further cell fractionation experiments and glycosylation tests indicated that OS-9 is a luminal ER protein. In vivo protein interaction analysis by fluorescence resonance energy transfer (FRET) showed no significant physical interaction of overexpressed PHD2-CFP and OS-9-YFP. We conclude that OS-9 plays no direct functional role in HIF degradation since physical interaction of OS-9 with oxygen sensing HIF prolyl hydroxylases cannot occur in vivo due to their different subcellular localization

Quantitative computed tomography and magnetic resonance imaging of the human pineal gland

Deckblatt Inhaltsverzeichnis 1 Einleitung 4 1\. 1 Aufbau und Funktion der menschlichen Zirbeldrüse 4 1\. 2 Melatonin 6 1\. 3 Schlafstörungen und Melatonin 10 1\. 4 Zirbeldrüsenverkalkung und Melatonindefizit 11 1\. 5 Radiologische Untersuchungen der Gl.pinealis 13 2 Material und Methoden 19 2\. 1 Zirbeldrüsen 19 2\. 2 Antropomorphes Phantom 20 2\. 3 CT-Messungen und Auswertung 22 2\. 4 MRT-Messungen und Auswertung 25 3 Ergebnisse 28 3\. 1 CT-Messungen 28 3.2 MR-Messung 36 4 Diskussion 42 5 Zusammenfassung 49 6 Anhang 51 7 Danksagung 54 8 LiteraturverzeichnisStand der Forschung und Fragestellung Mit zunehmendem Alter finden sich beim Menschen immer häufiger Zirbeldrüsenkonkremente. Die Melatoninproduktion kann dadurch beeinträchtigt werden. Mit Hilfe der Computertomographie kann das Volumen des unverkalkten Zirbeldrüsengewebes (UCPT, uncalcified pineal tissue) quantifiziert werden. In dieser Arbeit wurde der Einfluß der benutzten Schichtdicke auf die Reproduzierbarkeit solcher Messungen untersucht. Außerdem wurde der Zusammenhang zwischen der Signalintensität der Zirbeldrüsen auf MR- Aufnahmen und der Drüsenverkalkung erforscht. Material und Methoden Untersucht wurden 22 postmortal entnommene menschliche Zirbeldrüsen. Die computertomographische Bestimmung des Volumens des unverkalkten Drüsengewebes (UCPT) erfolgte nach der Methode von Kunz et al. Die 1mm-, 2mm-, 4mm- und 8mm- CT-Messungen wurden jeweils zweimal durchgeführt. Als Maß für die Reproduzierbarkeit (repeatability) wurde die Wertepaarvarianz (within-subject- variance) benutzt. Zur statistischen Auswertung dienten der Friedman-Test und der multiple Vergleich nach Wilcoxon und Wilcox. Die MR-Untersuchung jeder Drüse wurde jeweils nur einmal mit Hilfe dreier MR-Sequenzen durchgeführt. Als Maß für die Signalintensität auf MR-Aufnahmen diente das dimensionslose signal intensity ratio (SIR). Der Pearson- Korrelationskoeffizient diente zur statistischen Auswertung des Zusammenhangs zwischen dem SIR-Werten und dem computertomographisch ermittelten mittleren Dichtewerten der Drüsen. Ergebnisse Die 1mm-CT-Methode zeigte die beste Reproduzierbarkeit sowohl für die Drüsenvolumenmessung als auch für die UCPT-Messung. Die within-subject variance der Volumenmessung war 41,5 mm6 und die der UCPT-Messung 44 VU2(VU=volume units). Die 1mm-Messung unterscheidet sich signifikant von der 4mm- und der 8mm-Messung nicht aber von der 2mm-Messung. Bei keiner der drei hier benutzten MR-Sequenzen konnte ein signifikanter Zusammenhang zwischen SIR (signal intensity ratio) und dem computertomographisch ermittelten mittleren Dichtewert der Drüse gefunden. Schlussfolgerung Die Ergebnisse zeigen, daß die 1mm-Methode den 4mm- und 8mm-Methoden hinsichtlich der Reproduzierbarkeit überlegen ist. Die von uns benutzten MR-Sequenzen waren nicht für die Beurteilung der Zirbeldrüsenverkalkung geeignet.Rationale and Objectives Increasing pineal calcification can cause a relative melatonin deficite. Computed tomography can be used for quantifying the uncalcified pineal tissue volume (UCPT). Earlier studies had shown that the UCPT is positively and significantly associated with the excretion of the melatonine metabolite aMT6s in urine. The main purpose of this study was to estimate the influence of slice thickness on the repeatability of such CT- assisted measurements. Another aim of the study was to examine the relationship between the signal intensity of pineal glands on MR images and their level of calcification. Methods We examined 22 human pineal glands obtained at autopsy. Total pineal volume and uncalcified pineal tissue volume(UCPT) were estimated using a CT-assisted method developed by Kunz et al. CT measurements were repeated twice with a slice thickness of 1, 2, 4 or 8 mm. The within-subject variance of these repeated measurements is an estimate of their repeatability. The Friedman test and the Wilcoxon-Wilcox test were used to compare the repeatability of the different methods. Magnetic resonance imaging was used to measure the SIR (signal intensity ratio) of the pineal glands. SIR is the quotient of the signal intensity of the gland and the signal intensity of water. Each examination included measurements with three different MR sequences (one T2 weighted and two T1 weighted). For each sequence the SIR was compared with the mean radiographic density of the respecive glands using Pearson�s correlation coefficient. The mean radiographic density was calculated using the CT data. Results The 1mm-slice method had the best repeatability. In this case the within-subject variance of the volume measurement was 41,5 mm6 and the within-subject variance of the UCPT measurement was 44 VU2 (VU=Volume Units). The 1mm-slice method has a significantly better repeatability in comparison to the 4mm- and 8mm-methods (p<0,05). For all three MR sequences there was no significant correlation between SIR and mean radiographic density. Conclusions The repeatability of CT-assisted UCPT measurements is greatly influenced by slice thickness. 1mm slices offer a significantly improved repeatability in comparison to 4 mm or 8mm slices. The MR sequences used in this study proved to be unsuitable for the evaluation of pineal calcification