Easy Pulsatile Phantom for Teaching and Validation of Flow Measurements in Ultrasound.

PURPOSE: To build a simple model to teach and validate non-pulsatile and pulsatile flow quantification in ultrasound. MATERIALS AND METHODS: The setting consists of the following connected components: (1) medical syringe pump producing an adjustable constant flow (ml/min), (2) modulator modifying constant flow to a reproducible pulsatile flow, (3) water tank containing a diagonal running silicone tube (0.5 mm inner diameter), and (4) a fixated ultrasound probe (L9 Linear Array 9 MHz, GE Logiq E9) measuring the flow inside the tube. Commercially available microbubbles suspended with physiological saline solution were used for ultrasonic visibility. Spectral Doppler of different flow profiles is performed. RESULTS: The syringe pump produces an adjustable, constant flow and serves as the reference standard. The filling volume of the tube system is 1.2 ml. Microbubbles are very well detected by ultrasound and can be used as an easy and clean blood mimicking substance. The modulator generates different physiological and pathological flow profiles. Velocities are similar to those found within human blood vessels. Thus, it is possible to train and validate flow measurements in ultrasound. CONCLUSION: The model produces non-pulsatile and various pulsatile flow profiles and allows validation of flow measurements. The compact size permits easy and economic setup for flow measurements in research, skills lab and continuing education.

Which factors influence MRI-pathology concordance of tumour size measurements in breast cancer?

OBJECTIVES: To assess MRI-pathology concordance and factors influencing tumour size measurement in breast cancer. MATERIALS AND METHODS: MRI tumour size (greatest diameter in anatomical planes (MRI-In-Plane) and greatest diameter along main tumour axis (MRI-MPR)) of 115 consecutive breast lesions (59 invasive lobular carcinoma, 46 invasive ductal carcinoma, and 10 ductal carcinoma in situ) was retrospectively compared to size measured at histopathology (pT size (Path-TNM) and greatest tumour diameter as relevant for excision (Path-Diameter; reference standard)). Histopathological tumour types, preoperative palpability, surgical management, additional high-risk lesions, and BI-RADS lesion type (mass versus non-mass enhancements) were assessed as possible influencing factors. RESULTS: Systematic errors were most pronounced between MRI-MPR and Path-TNM (7.1 mm, limits of agreement (LoA) [-21.7; 35.9]), and were lowest between MRI-In-Plane and Path-Diameter (0.2 mm, LoA [-19.7; 20.1]). Concordance rate of MRI-In-Plane with Path-Diameter was 86% (97/113), overestimation 9% (10/113) and underestimation 5% (6/113); BI-RADS mass lesions were overestimated in 7% (6/81) versus 41% (13/32) for non-mass enhancements. On multivariate analysis only BI-RADS lesion type significantly influenced MRI-pathology concordance (p < 0.001). 2/59 (3%) ILC did not enhance. CONCLUSION: Concordance rate varies according to the execution of MRI and histopathological measurements. Beyond this only non-mass enhancement significantly predicted discordance. KEY POINTS: • Execution and scope of MRI and histopathological size measurements influence concordance rate. • Non-mass like enhancement predicts discordance. • Additional high-risk lesions in proximity of tumour do not cause measurement discordance. • Low percentage of ILC do not enhance at all.

Breast microcalcifications as type descriptors to stratify risk of malignancy: a systematic review and meta-analysis of 10665 cases with special focus on round/punctate microcalcifications.

PURPOSE: To use a systematic review and meta-analysis to determine the predictive value of five suspicious type descriptors of microcalcifications, with special focus on round/punctate microcalcifications because of controversy. MATERIALS AND METHODS: We performed a literature search using three databases and one search engine. We screened citations for malignancy rates of type descriptors. We regarded malignancy rates below 2% (BI-RADS 3) and above 95% (BI-RADS 5) as clinically significant threshold values for suspicion (BI-RADS 4). RESULTS: Forty studies from 14 countries with a total of 10,665 microcalcification lesions were included. The pooled malignancy rates were: coarse heterogeneous, 13% (95% confidence interval (95%-CI): 7 - 20%); amorphous or indistinct, 27% (95%-CI: 21-33%); pleomorphic, 50% (95%-CI: 43-58%); linear, 78% (95%-CI: 68 - 86%). The pooled malignancy rate of all round/punctate microcalcifications was 9% (95%-CI: 6-13%), for the subgroup follow-up it was 0,5% (95%-CI: 0.08-2.57%), and with histological verification it was 14% (95%-CI: 11-19%). Woman selection and consideration of additional suspicious image findings were reasons for between-study heterogeneity. Addition of ACR distribution descriptors diversified risk stratification, but did not alter BI-RADS assessment category. CONCLUSION: All suspicious type descriptors including round/punctate microcalcifications as well as combinations of type with suspicious distribution descriptors fell into BI-RADS assessment category 4. Exclusion of suspicious adjunct factors can direct clustered, round/punctate microcalcifications to a lower BI-RADS assessment category.

Induction of luciferase activity under the control of an hsp70 promoter using high-intensity focused ultrasound: combination of bioluminescence and MRI imaging in three different tumour models.

The in vivo temporal changes of luciferase activity were investigated under the control of an hsp70 promoter in three tumour models after the application of different intensities of high-intensity focused ultrasound (HIFU). Three cell lines, SCCVII, NIH3T3 and M21 were stably transfected with a plasmid containing the hsp70 promoter and luciferase reporter gene, and tumours were subcutaneously initiated into mice. At a size of 1300 ± 234 mm(3), the tumours were exposed to five intensities of continuous HIFU (802-1401-2157-3067-4133 W/cm(2)) for 20 sec. Bioluminescence and MR imaging were performed to assess luciferase activity and signal intensity changes in the tissue. The MRI scan protocol was pre- and post-contrast T1-wt-SE, T2-wt-FSE, DCE-MRI, diffusion-wt STEAM sequence, T2 relaxation time determination obtained on a 1.5-T GE MRI scanner. The NIH3T3 tumours showed the highest luciferase activity of 328.1 ± 7.1 fold at 24 h at a HIFU intensity of 3067 W/cm(2), the M21 tumours of 3.2 ± 0.6 fold 8 hours and the SCCVII tumours 2.9 ± 0.9 fold 4 hours post-HIFU at 2157 W/cm(2). The greatest increase in T2 signal intensity and T2 relaxation time of 20.7 ± 3.4% was seen in the SCCVII tumours. The highest contrast medium uptake of 10.1 ± 1.1% was noted in the M21 tumours, and 14.8 ± 1.9% in the SCCVII tumours. In all tumours, a significant increase in the diffusion coefficient was seen with increased HIFU intensity, the highest of which was 40.3 ± 4.1% in the SCCVII tumours. The three tumour cell lines stably transfected with the hsp70/luciferase gene showed differential luciferase activity, which peaked at different times after the application of HIFU and was dependant on tumour type and HIFU energy deposition.

A new method to assess ventricular wall stress in patients with heart failure and its relation to heart rate variability.

INTRODUCTION: Heart failure is characterized by an increase in cardiac load, wall stress and autonomic dysfunction. The neurohumoral imbalance arising from adrenergic activation and parasympathetic withdrawal is associated with worse prognosis. We addressed the hypothesis that an increased left ventricular (LV) wall stress as assessed by cardiac magnetic resonance imaging (CMR) in patients with heart failure is related to a depression of heart rate variability (HRV). METHODS: Cardiac function and mass were measured in 37 individuals with suspected cardiomyopathy using CMR imaging. A thick-walled sphere model was used to calculate ventricular wall stress. Time domain analysis of HRV was obtained by long-term Holter ECG. RESULTS: Standard deviation of both normal-to-normal (NN) intervals (SDNN) and average NN intervals over 5 minutes (SDANN-i) were negatively correlated with LV enddiastolic wall stress (r = 0.42, P < 0.01). SDNN and SDANN-i were severely decreased (P < 0.01) in patients with increased enddiastolic LV wall stress > 12 kPa (vs. normal range: < 4 kPa). CONCLUSION: A relation between increased cardiac wall stress and depressed heart rate variability was observed in patients with heart failure. CMR-based measurement of LV volume and mass is appropriate to calculate LV wall stress which should be considered not only as a potential prognostic determinant but also as therapeutic target.

B-type natriuretic peptide and wall stress in dilated human heart.

Background Although B-type natriuretic peptide (BNP) is used as complimentary diagnostic tool in patients with unknown thoracic disorders, many other factors appear to trigger its release. In particular, it remains unresolved to what extent cellular stretch or wall stress of the whole heart contributes to enhanced serum BNP concentration. Wall stress cannot be determined directly, but has to be calculated from wall volume, cavity volume and intraventricular pressure of the heart. The hypothesis was, therefore, addressed that wall stress as determined by cardiac magnetic resonance imaging (CMR) is the major determinant of serum BNP in patients with a varying degree of left ventricular dilatation or dysfunction (LVD). Methods A thick-walled sphere model based on volumetric analysis of the LV using CMR was compared with an echocardiography-based approach to calculate LV wall stress in 39 patients with LVD and 21 controls. Serum BNP was used as in vivo marker of a putatively raised wall stress. Nomograms of isostress lines were established to assess the extent of load reduction that is necessary to restore normal wall stress and related biochemical events. Results Both enddiastolic and endsystolic LV wall stress were correlated with the enddiastolic LV volume (r = 0.54, P < 0.001; r = 0.81, P < 0.001). LV enddiastolic wall stress was related to pulmonary pressure (capillary: r = 0.69, P < 0.001; artery: r = 0.67, P < 0.001). Although LV growth was correlated with the enddiastolic and endsystolic volume (r = 0.73, P < 0.001; r = 0.70, P < 0.001), patients with LVD exhibited increased LV wall stress indicating an inadequately enhanced LV growth. Both enddiastolic (P < 0.05) and endsystolic (P < 0.01) wall stress were increased in patients with increased BNP. In turn, BNP concentration was elevated in individuals with increased enddiastolic wall stress (>8 kPa: 587 +/- 648 pg/ml, P < 0.05; >12 kPa: 715 +/- 661 pg/ml, P < 0.001; normal < or =4 kPa: 124 +/- 203 pg/ml). Analysis of variance revealed LV enddiastolic wall stress as the only independent hemodynamic parameter influencing BNP (P < 0.01). Using nomograms with "isostress" curves, the extent of load reduction required for restoring normal LV wall stress was assessed. Compared with the CMR-based volumetric analysis for wall stress calculation, the echocardiography based approach underestimated LV wall stress particularly of dilated hearts. Conclusions In patients with LVD, serum BNP was increased over the whole range of stress values which were the only hemodynamic predictors. Cellular stretch appears to be a major trigger for BNP release. Biochemical mechanisms need to be explored which appear to operate over this wide range of wall stress values. It is concluded that the diagnostic use of BNP should primarily be directed to assess ventricular wall stress rather than the extent of functional ventricular impairment in LVD.

A new methodological approach to assess cardiac work by pressure-volume and stress-length relations in patients with aortic valve stenosis and dilated cardiomyopathy.

In experimental animals, cardiac work is derived from pressure-volume area and analyzed further using stress-length relations. Lack of methods for determining accurately myocardial mass has until now prevented the use of stress-length relations in patients. We hypothesized, therefore, that not only pressure-volume loops but also stress-length diagrams can be derived from cardiac volume and cardiac mass as assessed by cardiac magnetic resonance imaging (CMR) and invasively measured pressure. Left ventricular (LV) volume and myocardial mass were assessed in seven patients with aortic valve stenosis (AS), eight with dilated cardiomyopathy (DCM), and eight controls using electrocardiogram (ECG)-gated CMR. LV pressure was measured invasively. Pressure-volume curves were calculated based on ECG triggering. Stroke work was assessed as area within the pressure-volume loop. LV wall stress was calculated using a thick-wall sphere model. Similarly, stress-length loops were calculated to quantify stress-length-based work. Taking the LV geometry into account, the normalization with regard to ventricular circumference resulted in "myocardial work." Patients with AS (valve area 0.73+/-0.18 cm(2)) exhibited an increased LV myocardial mass when compared with controls (P<0.05). LV wall stress was increased in DCM but not in AS. Stroke work of AS was unchanged when compared with controls (0.539+/-0.272 vs 0.621+/-0.138 Nm, not significant), whereas DCM exhibited a significant depression (0.367+/-0.157 Nm, P<0.05). Myocardial work was significantly reduced in both AS and DCM when compared with controls (129.8+/-69.6, 200.6+/-80.1, 332.2+/-89.6 Nm/m(2), P<0.05), also after normalization (7.40+/-5.07, 6.27+/-3.20, 14.6+/-4.07 Nm/m(2), P<0.001). It is feasible to obtain LV pressure-volume and stress-length diagrams in patients based on the present novel methodological approach of using CMR and invasive pressure measurement. Myocardial work was reduced in patients with DCM and noteworthy also in AS, while stroke work was reduced in DCM only. Most likely, deterioration of myocardial work is crucial for the prognosis. It is suggested to include these basic physiological procedures in the clinical assessment of the pump function of the heart.

Relation of B-type natriuretic peptide to left ventricular wall stress as assessed by cardiac magnetic resonance imaging in patients with dilated cardiomyopathy.

Ventricular loading conditions are crucial determinants of cardiac function and prognosis in heart failure. B-type natriuretic peptide (BNP) is mainly stored in the ventricular myocardium and is released in response to an increased ventricular filling pressure. We examined, therefore, the hypothesis that BNP serum concentrations are related to ventricular wall stress. Cardiac magnetic resonance imaging (MRI) was used to assess left ventricular (LV) mass and cardiac function of 29 patients with dilated cardiomyopathy and 5 controls. Left ventricular wall stress was calculated by using a thick-walled sphere model, and BNP was assessed by immunoassay. LV mass (r = 0.73, p < 0.001) and both LV end-diastolic (r = 0.54, p = 0.001) and end-systolic wall stress (r = 0.66, p < 0.001) were positively correlated with end-diastolic volume. LV end-systolic wall stress was negatively related to LV ejection fraction (EF), whereas end-diastolic wall stress was not related to LVEF. BNP concentration correlated positively with LV end-diastolic wall stress (r = 0.50, p = 0.002). Analysis of variance revealed LV end-diastolic wall stress as the only independent hemodynamic parameter influencing BNP (p < 0.001). The present approach using a thick-walled sphere model permits determination of mechanical wall stress in a clinical routine setting using standard cardiac MRI protocols. A correlation of BNP concentration with calculated LV stress was observed in vivo. Measurement of BNP seems to be sufficient to assess cardiac loading conditions. Other relations of BNP with various hemodynamic parameters (e.g., EF) appear to be secondary. Since an increased wall stress is associated with cardiac dilatation, early diagnosis and treatment could potentially prevent worsening of the outcome.

[Secretin-enhanced magnetic resonance cholangiopancreaticography: value for the diagnosis of chronic pancreatitis]. / Sekretinstimulierte Magnetresonanzcholangiopankreaticografie (MRCP): Wertigkeit in der Diagnostik der chronischen Pankreatitis.

Endoscopic retrograde cholangiopancreaticography (ERCP) is the morphologic gold standard for the diagnosis of chronic pancreatitis. Magnetic Resonance Imaging (MRI) enables the visualization of not only the pancreatic duct but also the surrounding parenchyma using T2- and T1-weighted sequences before and after the application of a contrast agent. Moreover, it allows the depiction of ductal segments distal to a stenosis or occlusion. However, conventional Magnetic Resonance Cholangiopancreaticography (MRCP) was not able to achieve accuracy similar to that of ERCP. Despite many technological innovations, such as fast breath-hold acquisitions or respiratory-gated 3D sequences, this drawback could not be overcome. In recent years, secretin-enhanced MRCP has been used for the diagnosis of chronic pancreatitis. A recent study showed that secretin not only improves the visibility of the pancreatic duct and its side branches but it also enhances the diagnostic accuracy of MRCP. The sensitivity, specificity, and positive and negative predictive values were improved by the application of secretin. Moreover, the agreement between independent observers increased after the use of secretin. In addition, quantitative post-processing tools have been developed that enable the measurement of the exocrine pancreatic output non-invasively using secretin-enhanced MRCP. These tools facilitate applications, such as functional follow-up after pancreaticogastrostomy and pancreaticogastric anastomoses, evaluation of the functional status of the graft after pancreas transplantation and follow-up of pancreatic drainage procedures and duct disruption.

Bone metastases in vulvar cancer: a rare metastatic pattern.

Bone metastases from a vulvar carcinoma are exceptionally rare with only five reported cases in the literature. We report on a patient who was initially treated with radical vulvectomy and bilateral inguinal lymphadenectomy for a vulvar cancer (pT2, pN2 (6/37), M0; G2). Due to a positive nodal status, adjuvant radiation of the vulva and the pelvis was performed additionally. The patient presented 4 months after initial therapy with severe pain in the right humeral shaft due to a pathologic fracture based on an osteoclastic metastasis. During osteosynthetic stabilization histologic and immunohistochemical stain gave evidence of a metastasis of the known vulvar carcinoma. Bone scan showed enhancements in both humeral heads as well as the right distal femur, whereas plain radiographs confirmed further metastases in all suspected areas. In conclusion, bone metastases should be considered in the differential diagnoses of unclear osseous pain in women with a history of vulvar cancer. Immunohistochemical examinations might be important to depict the epithelial character of the tissue and allude to the metastatic nature of such rare lesions. The atypical location should alert the physician to suspect distant metastasis, rather than locoregional disease.

[Indirect MR venography: contrast medium protocols, postprocessing and combination in diagnosing pulmonary emboli with MRI]. / Indirekte MR-Phlebografie: Kontrastmittelprotokolle, Nachverarbeitung und Kombination mit Lungenemboliediagnostik in der MRT.

PURPOSE: Integration of MR venography in a comprehensive MR imaging protocol in patients with suspected pulmonary embolism (PE) and evaluation of contrast media dosage, timing and postprocessing for diagnostic accuracy. MATERIALS AND METHODS: Forty-eight consecutive inpatients with suspected PE or deep vein thrombosis were examined by MR venography according to one of the following protocols: protocol I: MR venography only, 0.25 mmol/kg body weight (BW) Gadopentate dimeglumine (Gd-DTPA) as single dose, bolus timing; protocol II: MR angiography of pulmonary arteries with a cumulative dosage of 0.25 mmol/kg contrast media, modification of coil setting for MR venography without further contrast media application; protocol III: as protocol II but with 0.125 mmol/kg BW, followed by MR venography. Signal-to-noise ratio, contrast-to-noise ratio, number of definable vascular segments and image quality were evaluated. The results were compared to conventional bilateral venography. RESULTS: All MR venography examinations were of diagnostic quality and the examination time was below 10 min. MR venography could be performed in all 48 patients compared to 43 of 48 patients for conventional venography. Significantly more superficial and deep veins of the leg could be visualized by MR venography (94 % compared to 83 % for conventional venography). Sensitivity and specificity were 100 % and 92 %, respectively. Quality differed significantly between 0.125 mmol/kg (protocol III) and 0.25 mmol/kg Gd-DTPA (protocols I and II) while timing did not influence quality (protocol I vs. II). CONCLUSION: An integrated MR diagnostic evaluation of pulmonary arteries and veins of the leg is feasible in patients with suspected PE. MR venography with 0.25 mmol/kg Gd-DTPA reliably depicts the venous system of the leg more completely than conventional venography with at least equivalent diagnostic confidence.

MR imaging of compartment syndrome of the lower leg: a case control study.

The aim of this study was to evaluate the use of MR imaging for diagnosis and therapy management of compartment syndromes. In total, 15 patients (5 with an imminent compartment syndrome and 10 with manifest compartment syndrome) underwent MR imaging with a variety of pulse sequences including fat suppression, magnetization transfer imaging, and intravenous gadopentetate dimeglumine (Gd-DTPA) administration. Early and late follow-up MR images were obtained. Manifest compartment syndromes showed swollen compartments with loss of normal muscle architecture on T1-weighted spin-echo images. T2-weighted spin-echo and magnetization transfer imaging showed bright areas, which enhanced after Gd-DTPA. Early follow-up showed changes in enhancement patterns; late follow-up showed fibrosis and cystic and fatty degenerations of the affected compartments. MR imaging can help make the diagnosis of a manifest compartment syndrome in clinically ambiguous cases. It points out the affected compartments and allows the surgeon to selectively split the fascial spaces.

[Biventricular MR volumetric analysis and MR flow quantification in the ascending aorta and pulmonary trunk for quantification of valvular regurgitation]. / Biventrikuläre MR-Volumetrie und MR-Flussmessungen in Aorta ascendens und Truncus pulmonalis zur Quantifizierung von Klappeninsuffizienzen.

PURPOSE: To test the value of biventricular volumetric analysis and the combination of biventricular volumetric analysis with flow quantification in the ascending aorta (Ao) and pulmonary trunk (Pu) for quantification of regurgitation volume and cardiac function in valvular regurgitation (VR) according to location and presence of single or multivalvular disease. MATERIALS AND METHODS: In 106 patients, the stroke volumes were assessed by measuring the biventricular volumes and the forward-stroke volumes in the great and small circulation by measuring the flow in the Ao and Pu. Valve regurgitation volumes and quotients were calculated for single and multivalvular disease and correlated with semiquantitative 2D-echocardiography (grade I-IV). For the assessment of the cardiac function in VR, the volumetric parameters of ejection fraction and end-diastolic (EDV) and end-systolic (ESV) volumes were determined. RESULTS: The detection rate was 49% for left ventricular (LV) VR and 42% for right ventricular (RV) VR. Low LV VR and RV VR usually could not be detected quantitatively, with the detection rate improving with echocardiographically higher insufficiency grades. Quantitative MRI could detect a higher grade solitary aortic valve insufficiency (> or = 2) in 11 of 12 patients and higher grade mitral valve insufficiency in 4 of 10 patients. A significant increase in RV and LV ventricular EDV and ESV was seen more often with increased MR regurgitation volumes. Aortic stenosis did not interfere with flow measurements in the Ao. CONCLUSIONS: Biventricular volumetry combined with flow measurements in Ao and Pu is a robust, applicable and simple method to assess higher grade regurgitation volumes and the cardiac function in single and multivalvular regurgitation at different locations. It is an important application for the diagnosis of VR by MRI.