Imaging Properties and Tumor Targeting of 68Ga-NeoBOMB1, a Gastrin-Releasing Peptide Receptor Antagonist, in GIST Patients.

Background: Gastrin-releasing peptide receptors (GRPRs) are molecular imaging targets in multiple malignancies. Recently, NeoBOMB1, a 68Ga-labelled antagonist to GRPRs, was developed for PET. Here we report the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) describing diagnostic properties and covariates influencing uptake of 68Ga-NeoBOMB1 in oligometastatic gastrointestinal stromal tumor (GIST) patients. Methods: Nine patients with advanced GIST using PET/CT (computed tomography) were included. After kit-based 68Ga-NeoBOMB1 preparation with a licensed 68Ge/68Ga generator, 3 MBq/kg body weight were injected intravenously. PET/CT included dynamic and static PET scans 5, 12 and 18 min and 1, 2, and 3−4 h post injection (first six patients) and static PET scans 2 and 3−4 h post injection (last three participants). Tumor targeting was assessed on a per-lesion and per-patient basis. Results: Six patients showed visible radiotracer uptake in at least one tumor lesion. Seventeen out of 37 tumor lesions exhibited significant 68Ga-NeoBOMB1 uptake (median SUVmax 11.8 [range 2.8−51.1] 2 h p.i. and 13.2 [range 2.5−53.8] 3−4 h p.i) and improved lesion-to-background contrast over time. Five lesions (13.5%) were identified only by 68Ga-NeoBOMB1-PET, with no correlation on contrast-enhanced CT. Three patients showed no radiotracer accumulation in any lesions. Tracer uptake correlated with male sex (p < 0.0001), higher body mass index (p = 0.007), and non-necrotic lesion appearance (p = 0.018). There was no association with whole-lesion contrast enhancement, hepatic localization, mutational status, or disease duration. Conclusions: 68Ga-NeoBOMB1-PET exhibits variable tumor uptake in advanced-stage GIST patients, correlating with lesion vitality based on CT contrast uptake, opening the possibility of a theragnostic approach in selected cases.

Extensor tendinopathy of the elbow assessed with sonoelastography: histologic correlation.

PURPOSE: To compare agreement between conventional B-mode ultrasound (US) and compression sonoelastography (SEL) of the common extensor tendons of the elbow with histological evaluation. MATERIALS AND METHODS: Twenty-six common extensor tendons were evaluated in 17 cadavers (11 females, median age 85 years and 6 males, median age 80 years). B-mode US was graded into: Grade 1, homogeneous fibrillar pattern; grade 2, hypoechoic areas and/or calcifications <30%; and grade 3 > 30%. SEL was graded into: Grade 1 indicated blue (hardest) to green (hard); grade 2 yellow (soft); and grade 3 red (softest). B-mode US, SEL, and a combined grading score incorporating both were compared to histological findings in 76 biopsies. RESULTS: Histological alterations were detected in 55/76 biopsies. Both modalities showed similar results (sensitivity, specificity, and accuracy 84%, 81%, and 83% for B-mode US versus 85%, 86%, and 86% for SEL, respectively, P > 0.3). However, a combination of both resulted in significant improvement in sensitivity (96%, P < 0.02) without significant change in specificity (81%, P < 0.3), yielding an improved overall accuracy (92%). CONCLUSION: Combined imaging of the extensor tendons with both modalities is superior to either modality alone for predicting the presence of pathologic findings on histology. KEY POINTS: • Combination of B-mode US and SEL proved efficiency in diagnosing lateral epicondylitis. • Combination of B-mode US and SEL in lateral epicondylitis correlates to histology. • Combination of both modalities provides improved sensitivity without loss of specificity.

Sonoelastography of the Common Flexor Tendon of the Elbow with Histologic Agreement: A Cadaveric Study.

Purpose To determine the correlation of the results of conventional B-mode ultrasonography (US) and compression sonoelastography with histologic results in common flexor tendons of the elbow in human cadavers. Materials and Methods Twenty-five common flexor tendons were evaluated in 16 fresh, unembalmed cadavers of 11 women with a median age of 85 years (range, 71-101 years) and five men with a median age of 78 years (range, 70-88 years). Informed consent was provided according to the last will of the donors. B-mode US results were classified as grade 1, normal tendon with homogeneous fibrillar pattern; grade 2, tendon thickening or hypoechoic areas and/or calcifications in less than 30% of the tendon; or grade 3, hypoechoic areas and/or calcifications greater than 30% of the tendon. Sonoelastographic results were grade 1, blue (hardest) to green (hard); grade 2, yellow (soft); and grade 3, red (softest). The intraclass correlation coefficient was calculated to determine agreement with histologic findings for each B-mode US, sonoelastographic, and combined B-mode US and sonoelastographic examination. Histologic results were grade 1, normal, with parallel fibrillar pattern; grade 2, mild tendinopathy, with cellular infiltration, angiogenesis, or fatty vacuoles; or grade 3, severe tendinopathy, with loss of parallel collagen structure and necrosis. Results Histologic alterations were detected in 44% (11 of 25) of biopsy specimens. Intraclass correlation with histologic results was 0.57 for B-mode US, 0.68 for sonoelastography, and 0.84 for the combination of the two approaches. Conclusion The addition of sonoelastography to B-mode US provided statistically significant improvement in correlation with histologic results compared with the use of B-mode US alone (P < .02). © RSNA, 2016 Online supplemental material is available for this article.

Meralgia paraesthetica: Ultrasound-guided injection at multiple levels with 12-month follow-up.

OBJECTIVES: To evaluate the efficacy of ultrasound (US)-guided injections around the lateral femoral cutaneous nerve (LFCN) at different levels in meralgia paraesthetica (MP) patients. METHODS: The study was approved by the university ethics committee and informed oral and written consent were obtained from all patients. Between June 2008 and August 2013, 20 patients with symptoms of MP, including nine men (mean age, 61.33 years) and 11 women (mean age 61.18 years), were treated with US-guided injection of steroids along the LFCN at three different levels in a mean of 2.25 sessions. A visual analogue scale (VAS) was used to measure symptoms before, immediately after and 12 months after treatment. RESULTS: Complete resolution of symptoms was documented in 15/20 patients (mean VAS decreased from 82 to 0), and partial resolution in the remaining five (mean VAS decreased from 92 to 42), which was confirmed at 12-month follow-up. By using the different levels of injection approach overall significantly better symptom relief was obtained (p < 0.05). CONCLUSION: The outcome of US-guided injection along the LFCN can be further improved by injections at different levels (p < 0.05), which was confirmed at 12-month long-term follow-up. KEY POINTS: Meralgia paraesthetica is an entrapment neuropathy of the lateral femoral cutaneous nerve. Ultrasound proved effective in diagnosis and in guiding injection therapy. Injection at the anterior superior iliac spine has been used previously. Multiple injections along the nerve course were used in this study. Long-term follow-up (12 months) confirmed the results.

Sonographic cross-sectional area measurement in carpal tunnel syndrome patients: can delta and ratio calculations predict severity compared to nerve conduction studies?

OBJECTIVE: To evaluate the accuracy of two different sonographic median nerve measurement calculations in predicting carpal tunnel syndrome (CTS) severity in a study population with clinically and electrophysiologically confirmed CTS. METHODS: 643 wrists of 427 patients (325 females and 102 males, age range: 17-90 years, mean ± SD: 57.9 ± 14.7) were included with CTS diagnosis based on clinical and nerve conduction studies (NCS). Cross-sectional area (CSA) measurement of the median nerve was performed at the carpal tunnel level (CSAc) and at the pronator quadratus muscle level (CSAp). Two parameters were calculated: delta (∆-CSA), which is the difference between proximal and distal measurements, and ratio (R-CSA), calculated by dividing distal over proximal measurements. RESULTS: Patients were classified into mild, moderate and severe CTS based upon NCS. The mean ∆-CSA (4.2 ± 2.6, 6.95 ± 2.2 and 10.7 ± 4.9 mm(2)) and mean R-CSA (1.5 ± 0.4, 1.95 ± 0.4 and 2.4 ± 0.7) values were significantly different between all groups (p < 0.001). Optimal cut-off values for ∆-CSA and R-CSA were 6 mm(2) and 1.7, respectively, to distinguish mild from moderate disease, and 9 mm(2) and 2.2, respectively, to distinguish moderate from severe disease. CONCLUSION: Threshold values for the calculated sonographic parameters ∆-CSA and R-CSA are useful in predicting CTS severity compared to NCS. KEY POINTS: • Two proposed parameters were calculated (∆-CSA, R-CSA) and compared to NCS. • A defined sonoanatomical proximal landmark was used for the calculation. • Both parameters showed ability to detect CTS severity comparable to NCS. • Cut-off values could be determined for both parameters.

Sonoelastography: musculoskeletal applications.

All participants for image samplings provided written informed consent. Conventional B-mode ultrasonography (US) has been widely utilized for musculoskeletal problems as a first-line approach because of the advantages of real-time access and the relatively low cost. The biomechanical properties of soft tissues reflect to some degree the pathophysiology of the musculoskeletal disorder. Sonoelastography is an in situ method that can be used to assess the mechanical properties of soft tissue qualitatively and quantitatively through US imaging techniques. Sonoelastography has demonstrated feasibility in the diagnosis of cancers of the breast and liver, and in some preliminary work, in several musculoskeletal disorders. The main types of sonoelastography are compression elastography, shear-wave elastography, and transient elastography. In this article, the current knowledge of sonoelastographic techniques and their use in musculoskeletal imaging will be reviewed.

Carpal tunnel syndrome: diagnosis by means of median nerve elasticity--improved diagnostic accuracy of US with sonoelastography.

PURPOSE: To compare the elasticity of the median nerve (MN) between healthy volunteers and patients with carpal tunnel syndrome (CTS) and to evaluate the diagnostic utility of sonoelastographic measurements of the elasticity of the MN. MATERIALS AND METHODS: This study was performed with institutional review board approval and written informed consent from all participants. Hands in 22 healthy volunteers and in 31 patients with symptomatic CTS were studied. The cross-sectional area (CSA) and the elasticity of the MN, which was measured as the acoustic coupler (AC)/MN strain ratio, were evaluated. RESULTS: Both hands in 22 healthy volunteers (three men [mean age, 52.7 years; age range, 41-65 years]; 19 women [mean age, 62.2 years; age range, 40-88 years]) and 43 hands in 31 patients with symptomatic CTS (three men [mean age, 69.0 years; age range, 46-88 years]; 28 women [mean age, 61.2 years; age range, 39-92 years]) were studied. Both the AC/MN strain ratio and the CSA in the patients with CTS were significantly higher than those in the healthy volunteers (P < .001). The presence of CTS was predicted by means of AC/MN strain ratio and CSA cutoff values, respectively, of 4.3 and 11 mm(2), with areas under the receiver operating characteristic curves (AUCs) of 0.78 (95% confidence interval [CI]: 0.69, 0.88) and 0.85 (95% CI: 0.78, 0.93). A logistic model that combined the AC/MN strain ratio and the CSA improved diagnostic accuracy for CTS, with an AUC of 0.91 (95% CI: 0.85, 0.97; P < .001). CONCLUSION: Sonoelastography provides significant improvement in the diagnostic accuracy of the ultrasonographic assessment of CTS.

Intracarpal tunnel contents: evaluation of the effects of corticosteroid injection with sonoelastography.

PURPOSE: To define the stiffness of the intracarpal tunnel contents and to evaluate the effect of corticosteroid injection on the intracarpal tunnel contents by using sonoelastography. MATERIALS AND METHODS: This study was conducted with the approval of the institutional review boards, and all participants provided written, informed consent. Both hands were studied in 20 healthy volunteers, including eight men (mean age, 59.6 years; range, 50-76 years) and 12 women (mean age, 61.0 years; range, 39-79 years) and 22 hands were studied in 20 patients with carpal tunnel syndrome (CTS) (five men [mean age, 49.0 years] and 15 women [mean age, 61.1 years]; range, 39-89 years) between April 2012 and August 2012. The stiffness of the intracarpal tunnel contents was estimated as the standardized acoustic coupler (AC)-to-intracarpal tunnel contents surrounding the nerve (AC/C) strain ratio, analyzed with the Mann-Whitney U test. The patients were treated with corticosteroid injections, and the strain ratio was reexamined 6 weeks later, analyzed with the Wilcoxon t test. RESULTS: The mean AC/C strain ratio in the CTS patients was 12.6 ± 4.7 (standard deviation), which was higher (stiffer) than that in the healthy volunteers with a mean strain ratio of 8.2 ± 3.5 (P = .0013). Six weeks after the injection, the mean AC/C strain ratio had decreased to 8.5 ± 4.1 (P = .00069, compared with the preinjection value) in the CTS patients. CONCLUSION: The stiffness of the intracarpal tunnel contents in untreated CTS patients is higher than that of healthy volunteers but decreases 6 weeks after corticosteroid injection.

Achilles tendon assessed with sonoelastography: histologic agreement.

PURPOSE: To compare and determine the level of agreement of findings at conventional B-mode ultrasonography (US) and sonoelastography of the Achilles tendon with findings at histologic assessment. MATERIALS AND METHODS: This study was conducted with the approval of the institutional review boards, and all cadavers were in legal custody of the study institution. Thirteen Achilles tendons in 10 cadavers (four male, six female; age range, 70-90 years) were examined with B-mode US and sonoelastography. B-mode US grading was as follows: Grade 1 indicated a normal-appearing tendon with homogeneous fibrillar echotexture; grade 2, a focal fusiform or diffuse enlarged tendon; and grade 3, a hypoechoic area with or without tendon enlargement. Sonoelastography grading was as follows: Grade 1 indicated blue (hardest) to green (hard); grade 2, yellow (soft); and grade 3, red (softest). Twenty-five biopsy specimens from representative lesions of the middle and distal thirds of the Achilles tendons were evaluated histologically. The concordance of B-mode US grading compared with sonoelastographic grading was assessed by using κ analysis. RESULTS: With B-mode US and sonoelastography, all 11 tendon thirds of histologically normal tendons were verified as normal (grade 1). Sonoelastography depicted 14 of 14 (100%) tendon thirds with histologic degeneration (grade 2 or 3), whereas B-mode US could depict only 12 of 14 (86%) lesions (grade 2 or 3). Only moderate agreement between B-mode US and sonoelastography was seen (κ = 0.52, P < .001). CONCLUSION: Sonoelastography might help predict signs of histopathologic degeneration of Achilles tendinosis, potentially more sensitively than B-mode US.

Greater trochanteric pain syndrome.

Pain around the greater trochanter is still a common clinical problem that may be secondary to a variety of either intra-articular or periarticular pathologies. Gluteal tendon pathologies are one of the primary causes of greater trochanteric pain, with attrition of the fasciae latae against the gluteus medius and minimus tendons, and the trochanteric bursa being possible causes. Key sonographic findings of gluteal tendinopathy, bursitis, and differential diagnosis are described in this overview. Clinical diagnosis and treatment of greater trochanteric pain syndrome is still challenging; therefore ultrasound is helpful to localize the origin of pain, determine underlying pathology, and, based on these findings, to guide local aspiration and/or injection in cases of tendinopathy and/or bursitis.

Sonographic criteria for therapy follow-up in the course of ultrasound-guided intra-articular injections of hyaluronic acid in hand osteoarthritis.

OBJECTIVE: To assess the value of sonographic criteria, based on measurements of joint capsule distension and synovial hyperemia, during the course of repeated ultrasound (US)-guided intra-articular injections of hyaluronic acid (HA) in hand osteoarthritis (OA). MATERIALS AND METHODS: Thirty-three patients (28 females/5 males), with hand OA in 78 joints, were included in this study. Patients underwent sonographic evaluation at baseline and consecutively for 4 weeks at weekly US-guided intra-articular injections of HA (Hyalgan(®)). Measurements of joint thickening and joint inflammation were performed with Grey-scale and semi-quantitative Power-Doppler US (PDUS). Sonographic values were correlated with weekly patients self-assessment of pain for each treated joint. RESULTS: The mean (SD) patients self-assessment of pain statistically significantly (p<0.0001) decreased from the first [68.3(22.3)] to the last week [37.3(30.34)]. A steady pain relief could be noticed in 67 (86%) of all treated joints. Over the whole observation period, the mean (SD) joint thickening of all joints markedly decreased from 15.6mm (5.3) to 13.1mm (6.4) (p<0.0001). The PDUS-score before initiation of HA treatment was statistically significantly higher than at the end of therapy (p<0.0001). The decrease in pain statistically significantly correlated with the decrease of joint thickening and PDUS-score between baseline and the end of therapy (p<0.001). CONCLUSION: In this study, we demonstrate the meaningfulness of sonographic evaluation criteria including measurements of joint capsule distension and PDUS vascularization, both significantly correlating with the decrease of pain, during the therapy follow-up of US-guided intra-articular HA-injections in patients with hand OA.

Comparison of image quality and radiation dose of different pulmonary CTA protocols on a 128-slice CT: high-pitch dual source CT, dual energy CT and conventional spiral CT.

OBJECTIVES: To compare image quality and radiation dose of high-pitch dual-source computed tomography (DSCT), dual energy CT (DECT) and conventional single-source spiral CT (SCT) for pulmonary CT angiography (CTA) on a 128-slice CT system. METHODS: Pulmonary CTA was performed with five protocols: high-pitch DSCT (100 kV), high-pitch DSCT (120 kV), DECT (100/140 kV), SCT (100 kV), and SCT (120 kV). For each protocol, 30 sex, age, and body-mass-index (mean 25.3 kg/m(2)) matched patients were identified. Retrospectively, two observers subjectively assessed image quality, measured CT attenuation (HU±SD) at seven central and peripheral levels, and calculated signal-to-noise-ratio (SNR) and contrast-to-noise-ratio (CNR). Radiation exposure parameters (CTDIvol and DLP) were compared. RESULTS: Subjective image quality was rated good to excellent in >92% (>138/150) with an interobserver agreement of 91.4%. The five protocols did not significantly differ in image quality, neither by subjective, nor by objective measures (SNR, CNR). By contrast, radiation exposure differed between protocols: significant lower radiation was achieved by using high-pitch DSCT at 100 kV (p < 0.01 in all). Radiation exposure of DECT was in between SCT at 100 kV and 120 kV. CONCLUSIONS: SCT, high-pitch DSCT, and DECT protocols techniques result in similar subjective and objective image quality, but radiation exposure was significantly lower with high-pitch DSCT at 100 kV. KEY POINTS: New CT protocols show promising results in pulmonary embolism assessment. High-pitch dual-source CT (DSCT) at 100 kV provides radiation dose savings for pulmonary CTA. High-pitch DSCT at 100 kV maintains diagnostic image quality for pulmonary CTA. Dual energy CT uses more radiation but also provides lung perfusion evaluation. Whether the additional perfusion data is worth the extra radiation remains undetermined.

Bifid median nerve in carpal tunnel syndrome: assessment with US cross-sectional area measurement.

PURPOSE: To evaluate the accuracy of ultrasonography (US) in the diagnosis of carpal tunnel syndrome (CTS) in patients with a bifid median nerve on the basis of cross-sectional area (CSA) measurements of the median nerve at the level of the carpal tunnel (CSAc), with additional measurements obtained more proximally (CSAp) at the level of the pronator quadratus muscle. MATERIALS AND METHODS: This HIPAA-compliant study was approved by the local institutional review board; informed oral and written consent were obtained. Fifty-three wrists in 49 consecutive patients with a bifid median nerve and CTS symptoms and 28 wrists in 27 healthy volunteers with a bifid median nerve were examined by using US. Two independent US examiners who were blinded to prior test results measured median nerve CSA at two levels, CSAc and CSAp. The difference between CSAc and CSAp (ΔCSA) was calculated for each wrist. Receiver operating characteristic (ROC) analysis was performed. RESULTS: The study population included 17 men and 32 women (mean age, 55.1 years; age range, 24-78 years). The control population included 13 men and 14 women (mean age, 52.6 years; age range, 24-86 years). Mean CSAc was approximately 5 mm(2) greater in patients with CTS than in healthy volunteers (P < .0001), while mean ΔCSA was 5.8-5.9 mm(2) greater in patients with CTS (P < .0001). A CSAc threshold of 12 mm(2) provided sensitivity and specificity of 84.9% and 46.5%, respectively, while a ΔCSA threshold of 4 mm(2) provided sensitivity and specificity of 92.5% and 94.6%, respectively. ROC analysis demonstrated a significant advantage of ΔCSA (area under ROC curve [A(z)] = 0.95-0.96) compared with CSAc (A(z) = 0.84-0.85) for the diagnosis of CTS (P < .003). CONCLUSION: The use of a ΔCSA parameter improves the diagnostic accuracy of US for the presence of CTS in patients with a bifid median nerve.

Entrapment neuropathies II: carpal tunnel syndrome.

Diagnostic tests in patients complaining of carpal tunnel syndrome (CTS) are based on physical examination, electrodiagnostic tests (EDTs), and diagnostic imaging. Timely diagnosis helps prevent permanent nerve damage and its sequelae in terms of functional impairment. Imaging provides additional information to that obtained from clinical tests and EDTs. By allowing direct visualization of the compressed median nerve (MN), ultrasound (US) and magnetic resonance imaging can depict the causes for secondary CTS and describe anatomical variants, such as a bifid MN or a persistent median artery of the forearm, as well as space-occupying lesions including tenosynovitis and ganglion cysts. In addition, diagnostic imaging is of value for postoperative patients presenting with persistent symptoms. Finally, US is able to add information for EDT-negative symptomatic patients. Over time, US has increased in its sensitivity and specificity so it can be used as the initial test in patients presenting with clinical symptoms of CTS because it is now equivalent to EDT. The use of US as a screening test may reduce the number of EDT examinations in patients with suspected CTS, providing additional valuable anatomical information.

Detection of vascularity in wrist tenosynovitis: power doppler ultrasound compared with contrast-enhanced grey-scale ultrasound.

INTRODUCTION: We sought to assess vascularity in wrist tenosynovitis by using power Doppler ultrasound (PDUS) and to compare detection of intra- and peritendinous vascularity with that of contrast-enhanced grey-scale ultrasound (CEUS). METHODS: Twenty-six tendons of 24 patients (nine men, 15 women; mean age ± SD, 54.4 ± 11.8 years) with a clinical diagnosis of tenosynovitis were examined with B-mode ultrasonography, PDUS, and CEUS by using a second-generation contrast agent, SonoVue (Bracco Diagnostics, Milan, Italy) and a low-mechanical-index ultrasound technique. Thickness of synovitis, extent of vascularized pannus, intensity of peritendinous vascularisation, and detection of intratendinous vessels was incorporated in a 3-score grading system (grade 0 to 2). Interobserver variability was calculated. RESULTS: With CEUS, a significantly greater extent of vascularity could be detected than by using PDUS (P < 0.001). In terms of peri- and intratendinous vessels, CEUS was significantly more sensitive in the detection of vascularization compared with PDUS (P < 0.001). No significant correlation between synovial thickening and extent of vascularity could be found (P = 0.089 to 0.097). Interobserver reliability was calculated to be excellent when evaluating the grading score (κ = 0.811 to 1.00). CONCLUSIONS: CEUS is a promising tool to detect tendon vascularity with higher sensitivity than PDUS by improved detection of intra- and peritendinous vascularity.

Is sonoelastography of value in assessing tendons?

Sonoelastography is a newly introduced ultrasound technique that evaluates tissue elasticity and thus provides additional information to that offered by conventional ultrasound images. In the musculoskeletal field, sonoelastography can help improve estimation of tendon stiffness. In this article, the principles and future developments of sonoelastography are discussed using the strongest and thickest tendon of the human body, the Achilles tendon, for illustrative purposes. Preliminary findings of sonoelastography in healthy and pathological Achilles tendons, technical considerations, examination technique and several limitations are addressed. The usefulness of elastography can be expected to increase rapidly in the musculoskeletal field, as soon as we learn to interpret elastographic artifacts as well as to take advantage of the new information provided by sonoelastography.

Caffeine and cognition in functional magnetic resonance imaging.

Caffeine has been consumed since ancient times due to its beneficial effects on attention, psychomotor function, and memory. Caffeine exerts its action mainly through an antagonism of cerebral adenosine receptors, although there are important secondary effects on other neurotransmitter systems. Recently, functional MRI (fMRI) entered the field of neuropharmacology to explore the intracerebral sites and mechanisms of action of pharmacological agents. However, as caffeine possesses vasoconstrictive properties it may interfere with the mechanisms underlying the functional contrast in fMRI. Yet, only a limited number of studies dealt with the effect of caffeine on measures in fMRI. Even fewer neuroimaging studies examined the effects that caffeine exerts on cognition: Portas and colleagues used fMRI in an attentional task under different levels of arousal (sleep deprivation or caffeine administration), concluding that the thalamus is involved in mediating the interaction of attention and arousal. Bendlin and colleagues found caffeine to stabilize the extent of neuronal activation in repetitive word stem completion, counteracting the general task practice effect. Recently, Koppelstaetter and colleagues assessed the effect of caffeine on verbal working memory demonstrating a modulatory effect of caffeine on brain regions (medial frontopolar and anterior cingulate cortex) that have been associated with attentional and executive functions. This review surveys and discusses neuroimaging findings on 1) how caffeine affects the contrast underlying fMRI techniques, particularly the blood oxygen level dependent contrast (BOLD fMRI), and 2) how caffeine operates on neuronal activity underlying cognition, to understand the effect of caffeine on behavior and its neurobiological underpinnings.

Inter- and intra-rater reproducibility of semiautomatic determination of volume parameters in cardiac magnetic resonance imaging.

PURPOSE: The purpose of this study was to evaluate inter- and intra-rater reproducibility in volume assessment using cardiac magnetic resonance imaging (CMRI). METHODS: Twenty-five healthy volunteers and 106 patients were included into this retrospective study and received CMRI. The patients were divided in three groups (group I, 80 patients with arrhythmia; group II, 20 patients with cardiomyopathy; group III, 6 patients after correction of septum defects). Therefore, the images were semiautomatically segmented by an experienced and an unexperienced radiologists. The analysis of end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV) as well as ejection fraction (EF) and myocardial mass (MM) were performed twice by an experienced and an unexperienced radiologists. The intra-class correlation coefficients (ICC) were determined for the evaluation of inter- and intra-rater variance. RESULTS: The intra-rater reproducibility for determination of EF, ESV, EDV and MM was excellent with ICCs ranging from 0.88 to 0.99 (all p<0.001). The inter-observer reproducibility for these parameters was also excellent with ICCs ranging from 0.91 to 0.98 (all p<0.001). The assessment of the SV showed an excellent intra-rater agreement with ICCs of 0.96 and 0.92 (both p<0.001), but only a moderate ICC for the inter-rater reproducibility (0.54, p<0.001). CONCLUSIONS: Our study shows that assessment of cardiac volumes can be performed on CMRIs with an excellent reproducibility by both experienced and unexperienced investigators.

High-energy phosphate metabolism in the calf muscle of healthy humans during incremental calf exercise with and without moderate cuff stenosis.

It is known that the relevance of a peripheral stenosis for muscle function increases with exercise. Our intention was to investigate the impact of a moderate cuff stenosis (CS) at 120 mmHg of the superficial femoral artery on high-energy phosphate (HEP) metabolism during isotonic, incremental calf exercise. Serial phosphorus 31 magnetic resonance spectroscopy (31P MRS) and velocity-encoded phase-contrast MR imaging (VEPC MRI) were carried out in each leg of ten healthy male volunteers. Each leg underwent four increments of calf exercise (2, 3, 4 and 5 W) followed by recovery during separate exercise sessions with and without a CS at 120 mmHg. The serial 31P MRS measurements had a time resolution of 10 s. VEPC MRI was performed at the end of each increment during separate sessions. During all increments, we detected significant differences (P < 0.05) in the phosphocreatine (PCr) time constants and the amount of PCr hydrolysis between the sessions without and with CS. Regarding the time courses of the PCr, inorganic phosphate (Pi) and pH level, we observed significant differences (P < 0.002) during exercise and recovery. During both conditions, the end-increment PCr levels as well as blood flow correlated significantly with the mechanical power. The PCr time constants during exercise significantly correlated with the intramuscular pH, but not with blood flow or mechanical power. However, the PCr recovery time constants correlated significantly with blood flow and end-exercise pH. Our study shows that reduction of blood flow due to a peripheral stenosis results in a prolongation of PCr time constants, decreased PCr and pH level as well as increased Pi level during exercise. We believe that 31P MRS during incremental exercise might provide additional information for assessing the relevance of a peripheral stenosis and its impact on muscle function.