Increased chondrocyte seeding density has no positive effect on cartilage repair in an MPEG-PLGA scaffold

Purpose

This study investigates the effect of cell seeding density on cartilage repair in matrix-assisted chondrocyte implantation in vitro and in vivo.

Methods

In vitro: Four different cell seeding densities of human chondrocytes were seeded onto a porous methoxy-polyethylene glycol-polylactic-co-glycolic acid scaffold (MPEG-PLGA) polymer scaffold ASEED? (1.2 × 10⁶, 4.0 × 10⁶, 1.2 × 10⁷ and 2.0 × 10⁷ cells/cm³). The cartilage repair response was evaluated by relative gene expression of the chondrogenic markers sox9, collagen types I, II and X, and aggrecan, total DNA content and sulphated glycosaminoglycan synthesis. In vivo: Using a New Zealand white rabbit intercondylar osteochondral defect model, three different cell seeding densities (1.2 × 10⁶, 4.0 × 10⁶ and 1.2 × 10⁷ cells/cm³) were tested with an empty scaffold as control. The cartilage repair response was evaluated using O’Driscoll score.

Results

In vitro: A significant difference (p < 0.05) in total DNA content was found at day 2 but not at day 7. The low cell seeding densities yielded the highest GAG content (p < 0.001) at day 7. Collagen type I was highest (p < 0.01) at the lowest density at day 7. In vivo: No significant difference was found between the 4 groups.

Conclusions

No positive effect on cartilage repair was found using increased cell seeding density.

Level of evidence

Controlled experimental study, Level II.     

Arguments for an increasing differentiation towards fibrocartilaginous components in midportion Achilles tendinopathy

Purpose

The objective of this study was to investigate the fibrocartilaginous differentiation occurring in midportion Achilles tendinopathy.

Methods

Tendon samples were retrospectively collected from 23 patients, who had undergone surgery for midportion Achilles tendinopathy resistant to conservative treatment. Based on histological scores, the biopts were subdivided into three categories: a light, moderate and severe histopathological stage. Throughout these stages, immunohistochemical staining was performed against biglycan, aggrecan and collagen type II, components characteristic for fibrocartilage. Staining of these components was evaluated using a semi-quantitative scoring method.

Results

The immunohistochemical scores of biglycan and aggrecan were statistically significant between the histopathological stages (P < 0.001). The immunohistochemical scores were positively correlated with the increasing histopathological stages [Spearman’s correlation coefficient = 0.93 for biglycan and 0.78 for aggrecan (P < 0.001)]. Staining for collagen type II remained negative throughout these stages.

Conclusion

Immunohistochemical staining of the fibrocartilaginous components biglycan and aggrecan showed a progressive increase, correlated with a further evolved histopathological stage. This observation gave arguments for an increased differentiation towards fibrocartilaginous components at protein level in midportion Achilles tendinopathy.

Level of evidence

III.     

A novel nano-structured porous polycaprolactone scaffold improves hyaline cartilage repair in a rabbit model compared to a collagen type I/III scaffold: in vitro and in vivo studies

Purpose

To develop a nano-structured porous polycaprolactone (NSP-PCL) scaffold and compare the articular cartilage repair potential with that of a commercially available collagen type I/III (Chondro-Gide^®) scaffold.

Methods

By combining rapid prototyping and thermally induced phase separation, the NSP-PCL scaffold was produced for matrix-assisted autologous chondrocyte implantation. Lyophilizing a water–dioxane–PCL solution created micro and nano-pores. In vitro: The scaffolds were seeded with rabbit chondrocytes and cultured in hypoxia for 6 days. qRT–PCR was performed using primers for sox9, aggrecan, collagen type 1 and 2. In vivo: 15 New Zealand White Rabbits received bilateral osteochondral defects in the femoral intercondylar grooves. Autologous chondrocytes were harvested 4 weeks prior to surgery. There were 3 treatment groups: (1) NSP-PCL scaffold without cells. (2) The Chondro-Gide^® scaffold with autologous chondrocytes and (3) NSP-PCL scaffold with autologous chondrocytes. Observation period was 13 weeks. Histological evaluation was made using the O’Driscoll score.

Results

In vitro: The expressions of sox9 and aggrecan were higher in the NSP-PCL scaffold, while expression of collagen 1 was lower compared to the Chondro-Gide^® scaffold. In vivo: Both NSP-PCL scaffolds with and without cells scored significantly higher than the Chondro-Gide^® scaffold when looking at the structural integrity and the surface regularity of the repair tissue. No differences were found between the NSP-PCL scaffold with and without cells.

Conclusion

The NSP-PCL scaffold demonstrated higher in vitro expression of chondrogenic markers and had higher in vivo histological scores compared to the Chondro-Gide^® scaffold. The improved chondrocytic differentiation can potentially produce more hyaline cartilage during clinical cartilage repair. It appears to be a suitable cell-free implant for hyaline cartilage repair and could provide a less costly and more effective treatment option than the Chondro-Gide^® scaffold with cells.     

Effects of perfusion and cyclic compression on in vitro tissue engineered meniscus implants

Purpose

The purpose of this study was to investigate the influence of continuous perfusion and mechanical stimulation on bone marrow stromal cells seeded on a collagen meniscus implant.

Methods

Bone marrow aspirates from 6 donors were amplified in vitro. 10⁶ human BMSC were distributed on a collagen meniscus implant. Scaffolds were cultured under static conditions (control) or placed into a bioreactor system where continuous perfusion (10?ml/min) or perfusion and mechanical stimulation (8?h of 10% cyclic compression at 0.5?Hz) were administered daily. After 24?h, 7 and 14?days, cell proliferation, synthesis of procollagen I and III peptide (PIP, PIIIP), histology, and the equilibrium modulus of the constructs were analyzed.

Results

Proliferation demonstrated a significant increase over time in all groups (p?<?0.001). PIP synthesis was found to increase from 0.1?±?0.0?U/ml/g protein after 24?h to 2.0?±?0.5 (perfusion), 3.8?±?0.3 (mechanical stimulation), and 1.8?±?0.2?U/ml/g protein (static control, lower than perfusion and mechanical stimulation, p?<?0.05). These differences were also evident after 2?weeks (2.7?±?0.3, 4.0?±?0.6, and 1.8?±?0.2?U/ml/g protein, p?<?0.01); PIIIP synthesis was found to increase from 0.1?±?0.0?U/ml/g protein after 24?h to 2.9?±?0.7 (perfusion), 3.1?±?0.9 (mechanical stimulation), and 1.6?±?0.3?U/ml/g protein (controls) after 1?week and remained significantly elevated under the influence of perfusion and mechanical stimulation (p?<?0.01) after 2?weeks. Mechanical stimulation increased the equilibrium modulus more than static culture and perfusion after 2?weeks (24.7?±?7.6; 12.3?±?3.7; 15.4?±?2.6?kPa; p?<?0.02).

Conclusion

Biomechanical stimulation and perfusion have impact on collagen scaffolds seeded with BMSCs. Cell proliferation can be enhanced using continuous perfusion and differentiation is fostered by mechanical stimulation.

Level of evidence

Non-applicable experimental study.     

Diffusion-weighted MR imaging for differentiating borderline from malignant epithelial tumours of the ovary: pathological correlation

Objectives

To investigate diffusion-weighted (DW) magnetic resonance (MR) imaging for differentiating borderline from malignant epithelial tumours of the ovary.

Methods

This retrospective study included 60 borderline epithelial ovarian tumours (BEOTs) in 48 patients and 65 malignant epithelial ovarian tumours (MEOTs) in 54 patients. DW imaging as well as conventional MR imaging was performed. Signal intensity on DW imaging was assessed and apparent diffusion coefficient (ADC) value was measured. The results were correlated with histopathology and cell density.

Results

The majority of MEOTs showed high signal intensity on DW imaging, whereas most BEOTs showed low or moderate signal intensity (P?=?0.000). The mean ADC value of the solid components in BEOTs (1.562?±?0.346?×?10^?3 mm²/s) was significantly higher than in MEOTs (0.841?±?0.209?×?10^?3 mm²/s). A threshold value of 1.039?×?10^?3 mm²/s permitted the distinction with a sensitivity of 97.0 %, a specificity of 92.2 % and an accuracy of 96.4 %. There was an inverse correlation between ADC value and cell density (r?=??0.609; P?=?0.0000) which was significantly lower in BEOTs than in MEOTs.

Conclusions

DW imaging is useful for differentiating borderline from malignant epithelial tumours of the ovary.

Key Points

? DW MR imaging is useful for differentiating BEOTs from MEOTs. ? Patients with BEOTs are treated differently from patients with MEOTs. ? Conservative fertility-sparing laparoscopic surgery can be performed in patients with BEOTs. ? BEOTs often affect young women of childbearing age.     

Diffusion-weighted imaging of focal renal lesions: a meta-analysis

Objectives

Contrast-enhanced MRI can only distinguish to a limited extent between malignant and benign focal renal lesions. The aim of this meta-analysis is to review renal diffusion-weighted imaging (DWI) to compare apparent diffusion coefficient (ADC) values for different renal lesions that can be applied in clinical practice.

Methods

A PubMed search was performed to identify relevant articles published 2004–2011 on renal DWI of focal renal lesions. ADC values were extracted by lesion type to determine whether benign or malignant. The data table was finalised in a consensus read. ADC values were evaluated statistically using meta-regression based on a linear mixed model. Two-sided P value <5 % indicated statistical significance.

Results

The meta-analysis is based on 17 studies with 764 patients. Renal cell carcinomas have significant lower ADC values than benign tissue (1.61?±?0.08?×?10^-3 mm²/s vs 2.10?±?0.09?×?10^-3 mm²/s; P?<?0.0001). Uroepithelial malignancies can be differentiated by lowest ADC values (1.30?±?0.11?×?10^-3 mm²/s). There is a significant difference between ADC values of renal cell carcinomas and oncocytomas (1.61?±?0.08?×?10^-3 mm²/s vs 2.00?±?0.08?×?10^-3 mm²/s; P?<?0.0001).

Conclusions

Evaluation of ADC values can help to determine between benign and malignant lesions in general but also seems able to differentiate oncocytomas from malignant tumours, hence potentially reducing the number of unnecessarily performed nephrectomies.

Key Points

? This meta-analysis assesses the role of diffusion-weighted MRI in renal lesions. ? ADC values obtained by DW MRI have been compared for different renal lesions. ? ADC values can help distinguish between benign and malignant tumours. ? Differentiating oncocytomas from malignant tumours can potentially reduce inappropriate nephrectomies.     

Contrast-enhanced ultrasound of focal nodular hyperplasia: a matter of size

Objectives

To assess the contrast-enhanced ultrasound (CEUS) frequencies of centrifugal enhancement, spoke-wheel sign and central scar in focal nodular hyperplasia (FNH) as a function of lesion size.

Methods

Ninety-four FNHs were retrospectively reviewed to assess their largest diameter and enhancement pattern, including centrifugal enhancement from one central artery, spoke-wheel sign, diffuse or centripetal enhancement, central scar and late-phase washout.

Results

Mean FNH-lesion size was 3.7?±?2.1 cm. Only 43.6 % of FNHs had centrifugal enhancement, with a spoke-wheel pattern (23.4 %) or without (20.2 %), while 56.4 % showed diffuse or centripetal enhancement. Centrifugal enhancement was observed in 73.9 % of FNHs ≤3.1 cm and 14.6 % of FNHs >3.1 cm (P?–4). Size and frequency of centrifugal enhancement were negatively correlated (r?=?–0.57, P?–4). The spoke-wheel pattern was also seen more frequently in smaller (37 %) than in larger FNHs (10.4 %) (P?–3). Late-phase washout was described in 5.3 % of FNHs and was not size-dependent. Lesions with a central scar were larger than those without, respectively, 5.7?±?1.7 and 3.6?±?2.0 cm (P?=?0.012).

Conclusions

Typical centrifugal enhancement yielding a confident FNH diagnosis is seen significantly more frequently when the lesion is ≤3.1 cm.

Key Points

? CEUS yields confident diagnoses of FNHs ≤3.1 cm ? The larger the FNH, the lower the diagnostic sensitivity of CEUS ? Final diagnosis of FNHs >3.1 cm should be obtained with MRI not CEUS     

Peripherally inserted central catheter placement in cancer patients with profound thrombocytopaenia: a prospective analysis

Objective

No studies have specifically evaluated the safety of peripherally inserted central catheter (PICC) placement in patients with profound thrombocytopaenia. We prospectively determined the frequency of haemorrhagic complications of PICC placement in cancer patients with uncorrected profound thrombocytopaenia.

Methods

Profound thrombocytopaenia was defined as a platelet count <50?×?10⁹/l. No patients received transfusions before or after the procedure. Three types of adverse effects were analysed: minor oozing, mild haematoma and major haemorrhage.

Results

One hundred and forty-three PICC implantations in 101 cancer patients were prospectively included in the study: seven patients (7 %) had a solid tumour and 94 (93 %) a haematological malignancy. Among these 143 procedures in thrombocytopaenic patients, 93 (65 %) were performed with a platelet count 20–50?×?10⁹/l and 50 (35 %) had lower than 20?×?10⁹/l. No major haemorrhage was observed. Minor oozing was observed in six implantations (4 %) and mild haematoma in two (1.5 %), for a total of eight minor haemorrhagic adverse events (5.5 %). In patients with a platelet count <20?×?10⁹/l, 1/50 (2 %) had minor oozing and none had minor haematoma.

Conclusions

In cancer patients with uncorrected profound thrombocytopaenia, the incidence of adverse events after PICC implantation was low, and was limited to minor haemorrhagic adverse events.

Key Points

? PICC placement has high technical success in profound thrombocytopaenic cancer patients. ? Few adverse events are encountered after PICC placement, limited to minor haemorrhage. ? PICC placement does not routinely require platelet transfusion in patients with thrombocytopaenia. ? Such PICC placement still seems safe when the platelet count is <20?×?10 ⁹ /l.     

Characterisation of solitary pulmonary lesions combining visual perfusion and quantitative diffusion MR imaging

Objective

To evaluate the diagnostic accuracy of dynamic contrast-enhanced (DCE) magnetic resonance (MR) and diffusion-weighted imaging (DWI) sequences for defining benignity or malignancy of solitary pulmonary lesions (SPL).

Methods

First, 54 consecutive patients with SPL, clinically staged (CT and PET or integrated PET-CT) as N0M0, were included in this prospective study. An additional 3-Tesla MR examination including DCE and DWI was performed 1 day before the surgical procedure. Histopathology of the surgical specimen served as the standard of reference. Subsequently, this functional method of SPL characterisation was validated with a second cohort of 54 patients.

Results

In the feasibility group, 11 benign and 43 malignant SPL were included. Using the combination of conventional MR sequences with visual interpretation of DCE-MR curves resulted in a sensitivity, specificity and accuracy of 100 %, 55 % and 91 %, respectively. These results can be improved by DWI (with a cut-off value of 1.52?×?10^?3 mm²/s for ADC_high) leading to a sensitivity, specificity and accuracy of 98 %, 82 % and 94 %, respectively. In the validation group these results were confirmed.

Conclusion

Visual DCE-MR-based curve interpretation can be used for initial differentiation of benign from malignant SPL, while additional quantitative DWI-based interpretation can further improve the specificity.

Key Points

? Magnetic resonance imaging is increasingly being used to help differentiate lung lesions. ? Solitary pulmonary lesions (SPL) are accurately characterised by combining DCE-MRI and DWI. ? Visual DCE-MRI assessment facilitates the diagnostic throughput in patients with SPL. ? DWI provides additional information in inconclusive DCE-MRI (type B pattern).     

Value of DW-MRI ADC quantification of colonic wall lesions in differentiation of inflammatory bowel disease and colorectal carcinoma

Purpose

The purpose of our study was to assess the efficiency of diffusion-weighted magnetic resonance imaging (DW-MRI) and the quantification of apparent diffusion coefficient (ADC) values in differentiating colorectal carcinoma from colonic inflammatory bowel disease (IBD) in cases with isolated colonic wall lesions and uncertain clinical and radiologic diagnostic criteria.

Methods

The study comprised 58 patients with segmental or focal isolated colonic wall thickening. All lacked satisfactory clinical–radiological findings for etiology determination. The mean ADC values of the thickened colonic walls were retrospectively compared with final histopathologic diagnoses. Receiver operating characteristic (ROC) curve analysis was used to determine the ADC cutoff value for differentiation.

Results

Mean ADC value in the colorectal carcinoma group was significantly lower than that in the IBD group: n = 27, 1.02 ± 0.26 × 10^?3 mm²/s; and n = 31, 1.53 ± 0.19 × 10^?3 mm²/s, respectively (P < 0.001). Cutoff ADC value for differentiating colorectal carcinoma from IBD was calculated as 1.39 × 10^?3 mm²/s, with 83.9 % sensitivity and 85.2 % specificity.

Conclusion

ADC measurement of the involved colonic wall segments with DW-MRI has the potential to differentiate isolated colonic IBD from colorectal carcinoma in cases in which clinical–radiologic findings are insufficient for a definitive diagnosis.     

Autologous chondrocyte implantation in children and adolescents

Purpose

Autologous chondrocyte implantation (ACI) is a well-established treatment method for cartilage defects in knees. Age-related grouping was based on expression data of cartilage-specific markers. Specificities of ACI in the different populations were analysed.

Methods

Two hundred and sixty-seven patients undergoing ACI in the knee between 2006 and 2010 were included in this analysis. Cell characteristics and expression data of cartilage-specific surface markers as CD44, aggrecan and collagen type II were statistically analysed for age association. Epidemiological data of the defined groups were compared. Course of treatment was evaluated using MRI.

Results

A correlation analysis showed statistically significant associations between age and aggrecan or collagen type II expression in all patients <30 years. A cluster analysis could predict age-dependent expression of these markers separating groups with an average age of 18.1 ± 2.3 and 23.6 ± 4.2 years, respectively (p < 0.02). Discriminance analysis suggested the age border between adults and juveniles at about 20 years. There was no influence of age on cell characteristics or CD44 expression. In the 19 of 267 patients with an age ≤18 years, gender distribution was not different compared to adults, but patella was significantly more affected. Cartilage lesions were mainly caused by osteochondritis dissecans (OCD) and trauma. The Knee Osteoarthritis Scoring System in MRI reached 4.8 ± 2.3 points before, declining to 3.3 ± 2.3 points 6 and 12 months after the operation.

Conclusions

Age-related expression of cartilage-specific markers allows definition of adolescents in cartilage regenerating surgery. Chondromalacia in these patients is mainly caused by OCD or trauma.

Level of evidence

Case series, Level IV.     

Detection of invasive components in cases of breast ductal carcinoma in situ on biopsy by using apparent diffusion coefficient MR parameters

Objectives

To evaluate whether apparent diffusion coefficient (ADC) parameters could identify invasive components in cases with ductal carcinoma in situ (DCIS) diagnosed by biopsy.

Methods

This retrospective study was approved by the institutional review board and the requirement to obtain informed consent was waived. Sixty-nine consecutive women with 70 lesions diagnosed with DCIS by biopsy underwent breast magnetic resonance (MR) imaging. Multiple regions of interest were placed (as many as possible) within the lesion on ADC maps. The minimum ADC values and the ADC difference values obtained as the difference between minimum and maximum ADCs were evaluated.

Results

Surgical specimens revealed 51 lesions with pure DCIS and the remaining 19 lesions with DCIS with invasive components (DCIS-IC). The minimum ADC value for DCIS-IC (0.99?±?0.04?×?10^?3 mm²/s) was significantly lower than that of pure DCIS (1.15?±?0.03?×?10^?3 mm²/s) (P??=??0.0037). The ADC difference value for DCIS-IC (0.38?±?0.05?×?10^?3 mm²/s) was significantly higher than that of pure DCIS (0.17?±?0.03?×?10^?3 mm²/s). ROC curve analysis for differentiating DCIS-IC from pure DCIS revealed that the area under the curve was 0.71 for minimum ADC value and 0.77 for ADC difference value.

Conclusions

The minimum ADC values and ADC difference values could suggest the presence of invasive components.

Key Points

? Identification of invasive components in DCIS before treatment is clinically important. ? Diffusion-weighted MR imaging can help lesion assessment in breast cancer. ? The minimum ADC value may suggest the presence of an invasive component in DCIS. ? The ADC difference value also suggests the presence of an invasive component in DCIS. ? Preoperative evaluation of diffusion-weighted MR imaging may help surgical planning for DCIS.     

Intravoxel incoherent motion MR imaging: comparison of diffusion and perfusion characteristics between nasopharyngeal carcinoma and post-chemoradiation fibrosis

Objectives

To compare the intravoxel incoherent motion (IVIM) diffusion and perfusion characteristics of nasopharyngeal carcinoma (NPC) and post-chemoradiation fibrosis to aid in their differentiation.

Methods

Fifty-three (64 %) patients with newly diagnosed NPC and 30 (36 %) patients with biopsy-proven post-chemoradiation fibrosis were recruited into tumour and fibrosis groups respectively. Diffusion-weighted magnetic resonance (MR) imaging was performed using 13 b values (0–1,000 s/mm²). Their respective IVIM parameters (D, pure diffusion; f, perfusion fraction; D*, pseudodiffusion coefficient) were obtained.

Results

D and f were significantly lower in NPC (D?=?0.752?±?0.194?×?10^-3 mm²/s, P <0.001; f?=?0.122?±?0.095, P <0.001) than in fibrosis (D?=?1.423?±?0.364?×?10^-3 mm²/s; f?=?0.190?±?0.120); while D* was significantly higher in NPC (111.366?±?65.528?×?10^-3 mm²/s, P <0.001) than in fibrosis (77.468?±?62.168?×?10^-3 mm²/s). Respective cut-off values with sensitivity, specificity and accuracy were: D?=?1.062?×?10^-3 mm²/s (100 %, 100 %, 100 %); f?=?0.132 (66.0 %, 100 %, 78.3 %); D*?=?85.283?×?10^-3 mm²/s (100 %, 90.7 %, 96.4 %).

Conclusion

NPC and post-chemoradiation fibrosis have distinctive IVIM parameters. IVIM MR imaging is potentially useful in discrimination between NPC and fibrosis.

Key Points

? New MRI techniques offer greater help in the assessment of nasopharyngeal carcinoma. ? Tumour and post-chemoradiation fibrosis have distinctive intravoxel incoherent motion diffusion/perfusion parameters. ? Non-invasive IVIM MRI may help differentiate between tumour and fibrosis. ? Pure diffusion is a robust independent discriminating factor which improves diagnostic confidence.     

Intravoxel incoherent motion perfusion imaging in acute stroke: initial clinical experience

Introduction

Intravoxel incoherent motion (IVIM) imaging is an MRI perfusion technique that uses a diffusion-weighted sequence with multiple b values and a bi-compartmental signal model to measure the so-called pseudo-diffusion of blood caused by its passage through the microvascular network. The goal of the current study was to assess the feasibility of IVIM perfusion fraction imaging in patients with acute stroke.

Methods

Images were collected in 17 patients with acute stroke. Exclusion criteria were onset of symptoms to imaging >5 days, hemorrhagic transformation, infratentorial lesions, small lesions <0.5 cm in minimal diameter and hemodynamic instability. IVIM imaging was performed at 3 T, using a standard spin-echo Stejskal-Tanner pulsed gradients diffusion-weighted sequence, using 16 b values from 0 to 900 s/mm². Image quality was assessed by two radiologists, and quantitative analysis was performed in regions of interest placed in the stroke area, defined by thresholding the apparent diffusion coefficient maps, as well as in the contralateral region.

Results

IVIM perfusion fraction maps showed an area of decreased perfusion fraction f in the region of decreased apparent diffusion coefficient. Quantitative analysis showed a statistically significant decrease in both IVIM perfusion fraction f (0.026?±?0.019 vs. 0.056?±?0.025, p?=?2.2?·?10^?6) and diffusion coefficient D compared with the contralateral side (3.9?±?0.79?·?10^?4 vs. 7.5?±?0.86?·?10^?4 mm²/s, p?=?1.3?·?10^?20).

Conclusion

IVIM perfusion fraction imaging is feasible in acute stroke. IVIM perfusion fraction is significantly reduced in the visible infarct. Further studies should evaluate the potential for IVIM to predict clinical outcome and treatment response.     

Characterization and therapy monitoring of head and neck carcinomas using diffusion-imaging-based intravoxel incoherent motion parameters—preliminary results

Introduction

Using the intravoxel incoherent motion (IVIM) model, diffusion-related coefficient (D) and perfusion-related parameter (f) can be measured. Here, we used IVIM imaging to characterize squamous cell carcinomas of head and neck (HNSCC) and evaluated its application in follow-up after nonsurgical organ preserving therapy.

Methods

Twenty-two patients with locally advanced HNSCC (clinical stage III to IVb) were examined before treatment using eight different b values (b?=?0, 50, 100, 150, 200, 250, 700, 800 s/mm²). All patients were followed for at least 7.5 months after conclusion of therapy. In 16 of these patients, follow-up MRI was available. Using the IVIM approach, f and D were extracted using a bi-exponential fit. For comparison, ADC maps were calculated.

Results

The initial values of f before therapy were located between 5.9 % and 12.9 % (mean: 9.4?±?2.4 %) except for two outliers (f?=?17.9 % and 18.2 %). These two patients exclusively displayed poor initial treatment response. Overall, high initial f (13.1?±?4.1 % vs. 9.1?±?2.4 %) and ADC (1.17?±?0.08?×?10^?3?mm²/s vs. 0.98?±?0.19?×?10^?3?mm²/s) were associated with poor short term outcome (n?=?6) after 7.5 months follow-up. D values before treatment were 0.98?×?10^?3?±?0.18 mm²/s and ADC values were 1.03?×?10^?3?±?0.18 mm²/s. At follow-up, in all primary responders, D (69?±?52 %), f (65?±?46 %), and ADC (68?±?49%) increased.

Conclusions

Our preliminary evaluation indicates that an initial high f may predict poor prognosis in HNSCC. In responders, a significant increase of all IVIM parameters after therapy was demonstrated.     

Quantification and characterisation of coronary artery plaque volume and adverse plaque features by coronary computed tomographic angiography: a direct comparison to intravascular ultrasound

Objective

We evaluated the performance of manual measures of coronary plaque volumes and atherosclerotic plaque features from coronary CT angiography (CTA), using intravascular ultrasound (IVUS) as the reference.

Methods

Thirty individual coronary plaques with suitable fiduciary markers were identified. Plaque volumes on coronary CTA were manually quantified by two observers and compared to IVUS plaque volumes as interpreted by an independent laboratory. The presence of adverse plaque characteristics—low attenuation plaque (LAP), positive remodelling (PR) and spotty calcification (SC)—on coronary CTA was evaluated and compared to IVUS.

Results

High correlation in plaque volumes was detected between observers (r?=?0.94, P?<?0.0001; 95 % limits of agreement <48.7 mm³, bias 6.6 mm³). Excellent correlation (r?=?0.95, P?<?0.0001) was noted in plaque volume between independent observers and IVUS (95 % limits of agreement <40.6 mm³, bias ?4.4 mm³) and did not differ from IVUS (105.0?±?56.7 vs. 109.4?±?60.7 mm³, P?=?0.2). The frequency of LAP (10 % vs. 17 %), PR (7 % vs. 10 %) and SC (27 % vs. 33 %) was similar between coronary CTA and IVUS (all P?=?NS).

Conclusions

Plaque volume on coronary CTA determined by manual methods demonstrates high correlation and modest agreement to IVUS. Further, coronary CTA demonstrates high accuracy for the identification of adverse plaque characteristics, including LAP, PR and SC.

Key Points

? Coronary CT angiography is a non-invasive test that enables coronary plaque assessment ? Plaque quantification by coronary CT angiography correlates well with intravascular ultrasound findings ? Coronary CT angiography can identify adverse plaque characteristics     

MRI-only lesions: application of diffusion-weighted imaging obviates unnecessary MR-guided breast biopsies

Objective

To assess if the application of diffusion-weighted imaging (DWI) obviates unnecessary MR-guided biopsies in suspicious breast lesions visible only on contrast-enhanced MRI (CE-MRI).

Methods

This institutional review board (IRB)-approved, retrospective, single-centre study included 101 patients (mean age, 49.5; SD 13.9 years) who underwent additional DWI at 1.5 T prior to MRI-guided biopsy of 104 lesions classified as suspicious for malignancy and visible on CE-MRI only. An experienced radiologist, blinded to histopathologic and follow-up results, measured apparent diffusion coefficient (ADC) values obtained from DWI. Diagnostic accuracy was investigated using receiver operating characteristics (ROC) analysis.

Results

Histopathology revealed 20 malignant and 84 benign lesions. Lesions were masses in 61 (15 malignant, 24.6 %) and non-masses in 43 cases (five malignant, 11.6 %). Mean ADC values were 1.53?±?0.38?×?10^?3 mm²/s in benign lesions and 1.06?±?0.27?×?10^?3 mm²/s in malignant lesions. ROC analysis revealed exclusively benign lesions if ADC values were greater than 1.58?×?10^?3 mm²/s. As a consequence, 29 false-positive biopsies (34.5 %) could have been avoided without any false-negative findings. Both in mass and in non-mass lesions, rule-in and rule-out criteria were identified using flexible ADC thresholds based on ROC analysis.

Conclusion

Additional application of DWI in breast lesions visible only on MRI can avoid false-positive, MR-guided biopsies. Thus, DWI should be an integral part of breast MRI protocols.

Key Points

? DWI measurements are a fast and helpful technique for improved breast lesion diagnosis ? DWI application in breast lesions visible only on MRI obviates false-positive, MR-guided biopsies ? Flexible ADC thresholds provide rule-in and rule-out criteria for breast lesion malignancy     

Quantitative analysis of diffusion-weighted magnetic resonance imaging in malignant breast lesions using different b value combinations

Objectives

To explore how apparent diffusion coefficients (ADCs) in malignant breast lesions are affected by selection of b values in the monoexponential model and to compare ADCs with diffusion coefficients (Ds) obtained from the biexponential model.

Methods

Twenty-four women (mean age 51.3 years) with locally advanced breast cancer were included in this study. Pre-treatment diffusion-weighted magnetic resonance imaging was performed using a 1.5-T system with b values of 0, 50, 100, 250 and 800 s/mm². Thirteen different b value combinations were used to derive individual monoexponential ADC maps. All b values were used in the biexponential model.

Results

Median ADC (including all b values) and D were 1.04?×?10^-3?mm²/s (range 0.82–1.61?×?10^-3?mm²/s) and 0.84?×?10^-3?mm²/s (range 0.17–1.56?×?10^-3?mm²/s), respectively. There was a strong positive correlation between ADCs and Ds. For clinically relevant b value combinations, maximum deviation between ADCs including and excluding low b values (<100 s/mm²) was 11.8 %.

Conclusion

Selection of b values strongly affects ADCs of malignant breast lesions. However, by excluding low b values, ADCs approach biexponential Ds, demonstrating that microperfusion influences the diffusion signal. Thus, care should be taken when ADC calculation includes low b values.

Key Points

? Diffusion-weighted sequences are increasingly used in breast magnetic resonance imaging ? Diffusion-weighting (b) values strongly influence apparent diffusion coefficients of malignant lesions ? Exclusion of low b values reduces the apparent diffusion coefficient ? Flow-insensitive monoexponential apparent diffusion coefficients approach biexponential diffusion coefficients     

Reduced cardiac 123I-metaiodobenzylguanidine uptake in patients with spinocerebellar ataxia type 2: a comparative study with Parkinson’s disease

Purpose

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder characterized by cerebellar ataxia, supranuclear ophthalmoplegia, and peripheral neuropathy. Autonomic nervous system dysfunction is often present. This study evaluated the cardiac sympathetic function in patients with SCA2 using ¹²³I-metaiodobenzylguanidine (MIBG) in comparison with patients with Parkinson’s disease (PD) and control subjects.

Methods

Nine patients with SCA2, nine patients with PD, and nine control subjects underwent ¹²³I-MIBG imaging studies from which early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates were calculated.

Results

Early (F?=?12.3, p?<?0.0001) and late (F?=?16.8, p?<?0.0001) H/M ratios were significantly different among groups. In controls, early and late H/M ratios (2.2?±?0.12 and 2.1?±?0.20) were significantly higher than in patients with SCA2 (1.9?±?0.23 and 1.8?±?0.20, both p?<?0.05) and with patients with PD (1.7?±?0.29 and 1.4?±?0.35, both p?<?0.001). There was also a significant difference in washout rates among groups (F?=?11.7, p?<?0.0001). In controls the washout rate (19.9?±?9.6 %) was significantly lower (p?<?0.005) than in patients with PD (51.0?±?23.7 %), but not different from that in SCA2 patients (19.5?±?9.4 %). In SCA2 patients, in a multivariable linear regression analysis only the Scale for the Assessment and Rating of Ataxia score was independently associated with early H/M ratio (β?=??0.12, p?<?0.05).

Conclusion

¹²³I-MIBG myocardial scintigraphy demonstrated an impairment of cardiac sympathetic function in patients with SCA2, which was less marked than in PD patients. These results suggest that ¹²³I-MIBG cardiac imaging could become a useful tool for analysing the pathophysiology of SCA2.     

Apparent diffusion coefficient of the vertebral bone marrow in children with Gaucher's disease type I and III

Purpose

To assess apparent diffusion coefficient (ADC) as a quantitative parameter for detection of vertebral bone marrow infiltration in children with Gaucher’s disease type I and III.

Material and methods

Prospective study was conducted on 20 infants and children (14 M, 6 F; aged 31–61 months; mean age 46 months) with Gaucher’s disease type I (n?=?13) and III (n?=?7), and 20 age and sex matched controls. They underwent routine and diffusion-weighted MR imaging of the lumbar spine using echo planar imaging with b value of 0, 500 and 1000 sec/mm2. The ADC value of the lumbar vertebral bone marrow was compared in different phenotypes and genotypes; and correlated with bone marrow burden score (BMB), chitotriosidase level, hemoglobin and platelet count.

Results

The mean ADC value of marrow infiltration in patients with Gaucher’s disease (0.39?±?0.06?×?10^?3 mm²/s) was significantly lower (P?=?0.001) than that of vertebral bone marrow in controls (0.54?±?0.05?×?10^?3 mm²/s). The cut-off ADC value used to differentiate patients with Gaucher’s disease from controls was (0.47?×?10^?3 mm²/s); with sensitivity of 95 %; specificity of 95 % and area under the curve of 0.986. The L444P/L444P mutation had significantly lower ADC value compared to other mutations (P?=?0.001). The mean ADC value of the bone marrow negatively correlated with BMB (r?=??0.831; P?=?0.001), and biomarkers of disease activity including chitotriosidase (r?=??0.542; P?=?0.014), hemoglobin (r?=??0.727; P?=?0.001) and platelets (r?=??0.698; P?=?0.001).

Conclusion

We concluded that there is significant difference in the ADC value of vertebral bone marrow between children with Gaucher’s disease and controls, and the ADC value correlated well with genotyping and some biomarkers of disease activity.