Dynamic Contrast-Enhanced Sonography and Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Preoperative Diagnosis of Infected Nonunions.

OBJECTIVES: Bone regeneration depends on perfusion of the fracture tissue, whereby hypervascularity is associated with infection, which itself causes nonunions. To date, nonunion perfusion has not been assessed with contrast-enhanced sonography. The aim of this study was to evaluate the potential of contrast-enhanced sonography in the analysis of nonunion tissue perfusion. METHODS: Nonunion vascularity of 31 patients before revision surgery was prospectively examined with qualitative contrast-enhanced sonography and dynamic contrast-enhanced magnetic resonance imaging (MRI). Time-intensity curves from 2-minute contrast-enhanced sonographic video clips were generated, and parameters such as wash-in rate, rise time, and peak enhancement were quantified. On dynamic contrast-enhanced MRI, the initial area under the enhancement curve was quantified. Preoperative radiographs, computed tomograms, the clinical nonunion score, laboratory infection features, as well as contrast-enhanced sonographic and dynamic contrast-enhanced MRI perfusion were correlated with microbiological results from the nonunion tissue. RESULTS: Both qualitative and quantitative contrast-enhanced sonography showed significant differences between infected and aseptic nonunions (P = .015 and .020). The qualitative dynamic contrast-enhanced MRI analysis was not significant (P= .244), but after quantification, a strong correlation (P = .007) with microbiological results was noted. A receiver operating characteristic analysis calculated ideal cutoff values for quantitative contrast-enhanced sonography and dynamic contrast-enhanced MRI so that their combination detected infected nonunions with sensitivity and specificity of 88.9% and 77.3%, respectively. Clinical, radiologic, and laboratory examinations did not correlate with microbiological results (P > .05). CONCLUSIONS: Contrast-enhanced sonography can visualize the vascularity of nonunions in real time, while quantification software allows for a semiobjective evaluation of bone perfusion. The correlations of both quantitative contrast-enhanced sonography and dynamic contrast-enhanced MRI with microbiological results show their high value for differentiation of infected from aseptic nonunions.

Dynamic contrast-enhanced magnetic resonance imaging: fundamentals and application to the evaluation of the peripheral perfusion.

INTRODUCTION: The ability to ascertain information pertaining to peripheral perfusion through the analysis of tissues' temporal reaction to the inflow of contrast agent (CA) was first recognized in the early 1990's. Similar to other functional magnetic resonance imaging (MRI) techniques such as arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) MRI, dynamic contrast-enhanced MRI (DCE-MRI) was at first restricted to studies of the brain. Over the last two decades the spectrum of ailments, which have been studied with DCE-MRI, has been extensively broadened and has come to include pathologies of the heart notably infarction, stroke and further cerebral afflictions, a wide range of neoplasms with an emphasis on antiangiogenic treatment and early detection, as well as investigations of the peripheral vascular and musculoskeletal systems. APPLICATIONS TO PERIPHERAL PERFUSION: DCE-MRI possesses an unparalleled capacity to quantitatively measure not only perfusion but also other diverse microvascular parameters such as vessel permeability and fluid volume fractions. More over the method is capable of not only assessing blood flowing through an organ, but in contrast to other noninvasive methods, the actual tissue perfusion. These unique features have recently found growing application in the study of the peripheral vascular system and most notably in the diagnosis and treatment of peripheral arterial occlusive disease (PAOD). REVIEW OUTLINE: The first part of this review will elucidate the fundamentals of data acquisition and interpretation of DCE-MRI, two areas that often remain baffling to the clinical and investigating physician because of their complexity. The second part will discuss developments and exciting perspectives of DCE-MRI regarding the assessment of perfusion in the extremities. Emerging clinical applications of DCE-MRI will be reviewed with a special focus on investigation of physiology and pathophysiology of the microvascular and vascular systems of the extremities.

Assessment of skeletal muscle microcirculation in type 2 diabetes mellitus using dynamic contrast-enhanced ultrasound: a pilot study.

PURPOSE: To investigate muscular micro-perfusion by employing dynamic contrast-enhanced ultrasound (CEUS) and performing transient arterial occlusion in patients with type 2 diabetes mellitus (DM-2). METHODS: Twenty DM-2 patients (mean age, 58 ± 8.6 years; duration of diabetes, 15.4 ± 12.1 years) and 20 healthy volunteers (mean age, 54 ± 5.4 years) participated. CEUS was applied to the calf, while 4.8 mL of SonoVue(®) was injected intravenously. At the thigh level, arterial occlusion (60 s) was performed. CEUS parameters (tmax, max, AUCpost and m) were evaluated and Pearson-product-moment correlation coefficients were computed. RESULTS: A moderate negative correlation of HbA1c and max was established (-0.53). Max in patients with DM-2 >10 years was 79.89 ± 37.4. Max in patients with DM-2 duration <10 years was 137.62 ± 71.72 (p = 0.04). AUCpost in patients with DM-2 duration >10 years was 3924.01 ± 1630.52. AUCpost in patients with DM-2 duration <10 years was 6453.59 ± 3206.23 (p = 0.04). CONCLUSION: Patients with long history of DM-2 present with impaired muscular perfusion. CEUS and transient arterial occlusion may provide appropriate methods for semi-quantitative evaluation of muscular micro-perfusion in patients with DM-2.

Hyperkalemic periodic paralysis and permanent weakness: 3-T MR imaging depicts intracellular 23Na overload--initial results.

PURPOSE: To assess whether myoplasmic ionic sodium (Na+) is increased in muscles of patients with hyperkalemic periodic paralysis (HyperPP) with 3-T sodium 23 (23Na) magnetic resonance (MR) imaging and to evaluate the effect of medical treatment on sodium-induced muscle edema. MATERIALS AND METHODS: This study received institutional review board approval; written informed consent was obtained. Proton (hydrogen 1 [1H]) and 23Na MR of both calves were performed in 12 patients with HyperPP (mean age, 48 years±14 [standard deviation]) and 12 healthy volunteers (mean age, 38 years±12) before and after provocation (unilateral cooling, one calf). 23Na MR included spin-density, T1-weighted, and inversion-recovery (IR) sequences. Total sodium concentration and normalized signal intensities (SIs) were evaluated within regions of interest (ROIs). Muscle strength was measured with the British Medical Research Council (MRC) grading scale. Five patients underwent follow-up MR after diuretic treatment. RESULTS: During rest, mean myoplasmic Na+ concentration was significantly higher in HyperPP with permanent weakness (40.7 µmol/g±3.9) compared with HyperPP with transient weakness (31.3 µmol/g±4.8) (P=.004). Mean SI in 23Na IR MR was significantly higher in HyperPP with permanent weakness (0.83±0.04; median MRC, grade 4; range, 3-5) compared with HyperPP without permanent weakness (0.67±0.05; median MRC, grade 5; range, 4-5) (P=.002). Provocation reduced muscle strength in HyperPP (before provocation, median MRC, 5; range, 3-5; after provocation, median MRC, 3; range, 1-4) and increased SI in 23Na IR from 0.75±0.09 to 0.86±0.10 (P=.004). Spin-density and T1-weighted sequences were less sensitive, particularly to cold-induced Na+ changes. 23Na IR SI remained unchanged in volunteers (0.53±0.06 before and 0.54±0.06 after provocation, P=.3). Therapy reduced mean SI in 23Na IR sequence from 0.85±0.04 to 0.64±0.11. CONCLUSION: 23Na MR imaging depicts increased myoplasmic Na+ in HyperPP with permanent weakness. Na+ overload may cause muscle degeneration developing with age. 23Na MR imaging may have potential to aid monitoring of medical treatment that reduces this overload.

3 Tesla sodium inversion recovery magnetic resonance imaging allows for improved visualization of intracellular sodium content changes in muscular channelopathies.

OBJECTIVES: To implement different sodium (²³Na)-magnetic resonance imaging (MRI) contrasts at 3 Tesla and to evaluate if a weighting toward intracellular sodium can be achieved, using 2 rare muscular channelopathies as model diseases. MATERIALS AND METHODS: Both lower legs of 6 patients with hypokalemic periodic paralysis (HypoPP), 5 patients with paramyotonia congenita (PC), and 5 healthy volunteers were examined on a 3 Tesla system with 3 different ²³Na-MRI pulse sequences. HypoPP and PC are rare muscle diseases, which are well characterized by elevated myoplasmic sodium at rest and after cooling, respectively. Intra- and interindividual comparisons were performed before and after provocation of one lower leg muscle. Three different ²³Na-MRI sequences were applied: (i) The total tissue sodium concentration was measured using a spin-density sequence (²³Na-TSC). (ii) A T1-contrast was applied to assess whether the known changes of the intracellular sodium concentration can be visualized by T1-weighting (²³Na-T1). (iii) An inversion recovery (²³Na-IR) sequence was used to utmost suppress the sodium signal from extracellular or vasogenic edema. Furthermore, a potential influence of the temperature dependency of the sodium relaxation times was considered. Additionally, H-MRI was performed to examine potential lipomatous or edematous changes. RESULTS: In HypoPP, all Na sequences showed significantly (P<0.05) higher signal intensities compared with PC patients and healthy subjects. In muscles of PC patients, provocation induced a significant (P=0.0007) increase (>20%) in the muscular ²³Na-IR signal and a corresponding decrease of muscle strength. Additionally, a tendency to higher ²³Na-T1 (P=0.07) and ²³Na-TSC (P=0.07) signal intensities was observed. Provocation revealed no significant changes in ¹H-MRI. In volunteers and in the contralateral, not cooled lower leg, there were no significant signal intensity changes after provocation. Furthermore, the ²³Na-IR sequence allows for a suppression of signal emanating from intravascular sodium and vasogenic edema. CONCLUSIONS: Our results indicate that the ²³Na-IR sequence allows for a weighting toward intracellular sodium. The combined application of the ²³Na-TSC and the ²³Na-IR sequence enables an improved analysis of pathophysiological changes that occur in muscles of patients with muscular channelopathies.

Dynamic contrast-enhanced ultrasound for assessment of skeletal muscle microcirculation in peripheral arterial disease.

OBJECTIVE: : This feasibility study was performed to assess whether dynamic contrast-enhanced ultrasound (CEUS) and transient arterial occlusion are able to detect alterations in the microvascular perfusion and arterial perfusion reserve in patients suffering from peripheral arterial disease (PAD) in comparison with healthy volunteers. MATERIALS AND METHODS: : Twenty patients with PAD, Rutherford classification grade I, category III (mean age, 64 years; mean height, 173 cm; mean weight, 81.8 kg), and 20 volunteers (mean age, 50 years; mean height, 174 cm; mean weight, 77.8 kg) participated in the study. Low-mechanical index CEUS (7 MHz; MI, 0.28) was performed to the dominant lower leg after start of a continuous automatic intravenous injection of 4.8 mL suspension with microbubbles containing sulfur hexafluoride (SonoVue) within 5 minutes. Perfusion of the calf muscle was monitored by CEUS before, during, and after release of arterial occlusion at the thigh level lasting for 60 seconds. Several parameters, especially the time to maximum enhancement after release of occlusion (tmax), the maximum enhancement after release of occlusion (maxenh), the total vascular response after release of occlusion (AUCpost), and the resulting slope (m2) to maximum enhancement were calculated. RESULTS: : After release of the occlusion, a significantly delayed increase of the CEUS signal to maxenh was observed in the patients with PAD (32 ± 17 seconds) compared with volunteers (17 ± 8 seconds, P = 0.0009). maxenh was 66.5 ± 36.6 (∼mL) in PAD versus 135.6 ± 75.1 (∼mL) in volunteers (P = 0.0016). AUCpost was 3016.5 ± 1825.8 (∼mL·s) in PAD versus 5906.4 ± 3173.1 (∼mL·s) in volunteers (P = 0.0013), and m2 was significantly lower in PAD (3.8 ± 5.2 vs. 14.8 ± 9.7 [∼mL/s], P = 0.0001). CONCLUSIONS: : Microvascular perfusion deficits and reduced arterial perfusion reserve in patients with PAD are clearly detectable with dynamic CEUS after transient arterial occlusion.

Comparison of transient arterial occlusion and muscle exercise provocation for assessment of perfusion reserve in skeletal muscle with real-time contrast-enhanced ultrasound.

OBJECTIVE: Contrast-enhanced ultrasound (CEUS) is able to quantify muscle perfusion and changes in perfusion due to muscle exercise in real-time. However, reliable measurement of standardized muscle exercise is difficult to perform in clinical examinations. We compared perfusion reserve assessed by CEUS after transient arterial occlusion and exercise to find the most suitable measurement for clinical application. METHODS: Contrast pulse sequencing (7 MHz) during continuous IV infusion of SonoVue(®) (4.8 mL/300 s) was used in 8 healthy volunteers to monitor muscle perfusion of the gastrocnemius muscle during transient (1 min) arterial occlusion produced by a thigh cuff of a venous occlusion plethysmograph. Isometric muscle exercise (50% of individual maximum strength for 20s) was subsequently performed during the same examination, and several CEUS parameters obtained from ultrasound-signal-intensity-time curves and its calculation errors were compared. RESULTS: The mean maximum local blood volume after occlusion was 13.9 [∼mL] (range, 4.5-28.8 [∼mL]), and similar values were measured after sub-maximum exercise 13.8 [∼mL], (range, 4.6-22.2 [∼mL]. The areas under the curve during reperfusion vs. recovery were also similar (515.2±257.5 compared to 482.2±187.5 [∼mLs]) with a strong correlation (r=0.65), as were the times to maximum (15.3s vs. 15.9s), with a significantly smaller variation for the occlusion method (±2.1s vs. ±9.0s, p=0.03). The mean errors for all calculated CEUS parameters were lower for the occlusion method than for the exercise test. CONCLUSIONS: CEUS muscle perfusion measurements can be easily performed after transient arterial occlusion. It delivers data which are comparable to CEUS measurements after muscle exercise but with a higher robustness. This method can be easily applied in clinical examination of patients with e.g. PAOD or diabetic microvessel diseases to assess perfusion reserve.

Functional imaging in muscular diseases.

OBJECTIVE: The development of morphological and functional imaging techniques has improved the diagnosis of muscular disorders. METHODS: With the use of whole-body magnetic resonance imaging (MRI) the possibility of imaging the entire body has been introduced. In patients with suspected myositis, oedematous and inflammatory changed muscles can be sufficiently depicted and therefore biopsies become more precise. RESULTS: Functional MR methods visualise different aspects of muscular (patho)physiology: muscular sodium (Na(+)) homeostasis can be monitored with (23)Na MRI; the muscular energy and lipid metabolism can be monitored using (31)P and (1)H MR spectroscopy. (23)Na MRI has reached an acceptable value in the diagnosis and follow-up of patients with muscular Na(+) channelopathies that are characterised by myocellular Na(+) overload and consecutive muscle weakness. Besides MRI, low mechanical index contrast-enhanced ultrasound (CEUS) methods have also been introduced. For evaluation of myositis, CEUS is more efficient in the diagnostic work-up than usual b-mode ultrasound, because CEUS can detect the inflammatory-induced muscular hyperperfusion in acute myositis. Moreover, the arterial perfusion reserve in peripheral arterial disease can be adequately examined using CEUS. CONCLUSION: Modern muscular imaging techniques offer deeper insights in muscular (patho)physiology than just illustrating unspecific myopathic manifestations like oedematous or lipomatous changes, hypertrophy or atrophy.

64-Multidetector-row spiral CT in pulmonary embolism with emphasis on incidental findings.

AIM: In this retrospective study, we assess the current role and future potential of computed tomography (CT) in the diagnostic algorithm of acute pulmonary embolism (PE). MATERIALS AND METHODS: Two hundred patients underwent 64-multidetector-row spiral CT of the chest, pelvis, and thigh for suspected PE. CT scans were reviewed, and the degree of contrast enhancement and the presence of PE and/or (deep) venous thrombosis were recorded. In the case of PE, the level of thrombus was noted as central, main, or lobar. If the scan yielded a positive result for thrombosis, intravenous localization was also determined. Patient age, length of admission, clinical course, clinical indication, and incidental findings were registered as well. RESULTS: PE was detected in 60 of the 200 patients with a high clinical probability of having PE (30%). Thirty-four patients had a positive CT scan result for venous thrombosis (17%). Twenty-four of the 60 patients had proximal deep venous thrombosis (40%), and 2 patients had arm venous thrombosis (3%). Thirty-four of the 60 patients had PE without venous thrombosis (57%). Eight of the 200 patients had deep venous thrombosis without suspicion of PE (4%). The distribution of the proximal thrombi showed 15 in a central artery (25%), 13 in a main pulmonary artery (22%), and 32 in a lobar segmental artery (53%). There was diffuse allocation of the thrombus in all lobes. Furthermore, CT scan noted a total of 120 incidental findings. CONCLUSION: Our study indicates the potential clinical use of a diagnostic strategy for ruling out PE based on D-dimer testing and multidetector-row CT. A larger outcome study is needed before this approach can be adopted.

Detection of gastrointestinal bleeding by using multislice computed tomography--acute and chronic hemorrhages.

Nowadays, computed tomography (CT) is established for diagnosing gastrointestinal bleeding. In this retrospective study, the use of CT in diagnosing gastrointestinal bleeding was evaluated. Fifty-three patients received a contrast-medium-enhanced helical multislice CT (MSCT) to locate the bleeding site. Seventy-nine percent of the hemorrhage were acute gastrointestinal bleedings. Fifty-five percent of the acute hemorrhages were located via helical MSCT, 45% of the chronic bleeding sites were detected. Notably, bleeding of diverticula, tumors, and angiodysplasias were well demonstrated. In conclusion, contrast-medium-enhanced MSCT may be used effectively as a noninvasive diagnostic tool for detecting gastrointestinal bleedings.