Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells

Purpose Cell-based therapy by transplantation of progenitor cells has emerged as a promising development for organ repair, but non-invasive imaging approaches are required to monitor the fate of transplanted cells. Radioactive labelling with ¹¹¹In-oxine has been used in preclinical trials. This study aimed to validate ¹¹¹In-oxine labelling and subsequent in vivo and ex vivo detection of haematopoietic progenitor cells. Methods Murine haematopoietic progenitor cells (10⁶, FDCPmix) were labelled with 0.1 MBq (low dose) or 1.0 MBq (high dose) ¹¹¹In-oxine and compared with unlabelled controls. Cellular retention of ¹¹¹In, viability and proliferation were determined up to 48 h after labelling. Labelled cells were injected into the cavity of the left or right cardiac ventricle in mice. Scintigraphic images were acquired 24 h later. Organ samples were harvested to determine the tissue-specific activity. Results Labelling efficiency was 75 ± 14%. Cellular retention of incorporated ¹¹¹In after 48 h was 18 ± 4%. Percentage viability after 48 h was 90 ± 1% (control), 58 ± 7% (low dose) and 48 ± 8% (high dose) (p<0.0001). Numbers of viable cells after 48 h (normalised to 0 h) were 249 ± 51% (control), 42 ± 8% (low dose) and 32 ± 5% (high dose) (p<0.0001). Cells accumulated in the spleen (86.6 ± 27.0% ID/g), bone marrow (59.1 ± 16.1% ID/g) and liver (30.3 ± 9.5% ID/g) after left ventricular injection, whereas most of the cells were detected in the lungs (42.4 ± 21.8% ID/g) after right ventricular injection. Conclusion Radiolabelling of haematopoietic progenitor cells with ¹¹¹In-oxine is feasible, with high labelling efficiency but restricted stability. The integrity of labelled cells is significantly affected, with substantially reduced viability and proliferation and limited migration after systemic transfusion.     

Postmortem redistribution of ketamine in ocular matrices: A study of forensic relevance

The present study evaluates the postmortem redistribution of ketamine in ocular matrices, such as vitreous humor, aqueous humor, and ocular tissues in an animal model. To understand the redistribution of ketamine and its metabolite (norketamine) in the ocular matrices, an in vivo study was performed in rabbits. The rabbits were divided into two groups: perimortem and postmortem. The postmortem samples were collected at 17 h after the administration of ketamine (40 mg/kg) intravenously. For a better understanding of the metabolism of ketamine in eyes, an ex vivo study was conducted in goat eyes after administration of ketamine intravitreally. The samples were analyzed by LC-MS/MS and the levels of ketamine and norketamine in these matrices were compared with that of whole blood and plasma. The results of the in vivo study showed a decrease in ketamine levels in whole blood and plasma while an increase in ocular matrices at postmortem. Though, in most cases, this increase/decrease was statistically insignificant. Moreover, there was an increase of norketamine level in ocular matrices. Ex vivo study also shows the presence of norketamine in ocular matrices of goat eyes. The presence of norketamine in goat eyes may be indicative of the metabolism of ketamine in the eyes.     

Gd-BOPTA for assessment of myocardial viability on MRI: changes of T1 value and their impact on delayed enhancement

Gadobenate (Gd-BOPTA), injected at a dose of 0.1 mmol/kg body weight, was compared with gadopentetate (Gd-DTPA), injected at a dose of 0.2 mmol/kg body weight, for delineation of myocardial infarction interindividually in two groups of 26 patients each. Delayed enhancement images were assessed subjectively for image quality, and measured for regional T1 values before, 3 min after and 25 min after the injection of each contrast agent. In the 26 patients who received Gd-BOPTA, T1 values of remote myocardium were 1,070 ± 125 ms, 358 ± 78 ms and 562 ± 108 ms before, 3 min after and 25 min after injection, respectively. Infarcted myocardium values were 1,097 ± 148 ms, 246 ± 68 ms and 373 ± 84 ms and left ventricular blood pool 1,238 ± 95 ms, 194 ± 47 ms and 373 ± 72 ms. In the 26 patients who received Gd-DTPA, T1 values were 1,087 ± 96 ms, 325 ± 60 ms and 555 ± 108 ms for remote myocardium; 1,134 ± 109, 210 ± 43 ms and 304 ± 57 ms for infarcted myocardium; and 1,258 ± 104 ms, 166 ± 27 ms and 351 ± 73 ms for left ventricular blood pool. Delayed enhancement image quality showing myocardial infarction was rated good (54%) and excellent (46%) after Gd-BOPTA, and good (58%) and excellent (42%) after Gd-DTPA (no significant differences). A single dose of Gd-BOPTA compared with a double dose of Gd-DTPA causes similar changes of T1 values in infarcted and remote myocardium and provides fairly similar contrast between infarcted and remote myocardium (0.64 ± 14 versus 0.71 ± 11) and slightly higher contrast between left ventricular blood and infarcted myocardium (0.22 ± 17 versus 0.14 ± 6; p < 0.05). Administration of 0.1 mmol/kg body weight Gd-BOPTA can provide similar late enhancement images compared with the standard 0.2 mmol/kg body weight dose of Gd-DTPA due to the higher T1 relaxivity associated with the former. Peter Lodemann is an employee of Bracco Deutschland GmbH.     

Predictive value of brain perfusion SPECT for ketamine response in hyperalgesic fibromyalgia

Purpose Ketamine has been used successfully in various proportions of fibromyalgia (FM) patients. However, the response to this specific treatment remains largely unpredictable. We evaluated brain SPECT perfusion before treatment with ketamine, using voxel-based analysis. The objective was to determine the predictive value of brain SPECT for ketamine response. Methods Seventeen women with FM (48 ± 11 years; ACR criteria) were enrolled in the study. Brain SPECT was performed before any change was made in therapy in the pain care unit. We considered that a patient was a good responder to ketamine if the VAS score for pain decreased by at least 50% after treatment. A voxel-by-voxel group analysis was performed using SPM2, in comparison to a group of ten healthy women matched for age. Results The VAS score for pain was 81.8 ± 4.2 before ketamine and 31.8 ± 27.1 after ketamine. Eleven patients were considered “good responders” to ketamine. Responder and non-responder subgroups were similar in terms of pain intensity before ketamine. In comparison to responding patients and healthy subjects, non-responding patients exhibited a significant reduction in bilateral perfusion of the medial frontal gyrus. This cluster of hypoperfusion was highly predictive of non-response to ketamine (positive predictive value 100%, negative predictive value 91%). Conclusion Brain perfusion SPECT may predict response to ketamine in hyperalgesic FM patients.     

64-Slice spiral computed tomography of the coronary arteries: dose reduction using an optimized imaging protocol including individual weight-adaptation of voltage and current–time product

Radiation dose and image quality were compared between a standard protocol (40 patients, group A) and a weight-adapted protocol of voltage and current–time product (44 patients, group B) using 64-slice coronary multidetector computed tomography (MDCT). Effective dose estimate was lower by 37% in all patients of group B (9.2 ± 2.5 mSv) compared with group A (14.6 ± 2.3 mSv, P < 0.0001). Group B patients with a small body mass index (BMI) benefited most with a dose reduction of 53% (6.7 ± 1.5 mSv in group B versus 14.1 ± 1.8 mSv in group A, P < 0.0001). Moderate reductions of 32% and 20% were achieved for patients with a medium and large BMI, respectively. Reduction in radiation dose did not affect the image quality as assessed by image noise, signal-to-noise ratios, and number of coronary segments with good diagnostic image quality. Individual weight-adaptation of voltage and current–time product significantly reduces the radiation dose without loss of image quality.     

Outcome of long-axis percutaneous sacroplasty for the treatment of sacral insufficiency fractures

Our aim was to assess the clinical outcome of patients who were subjected to long-axis sacroplasty for the treatment of sacral insufficiency fractures. Nineteen patients with unilateral (n = 3) or bilateral (n = 16) sacral fractures were involved. Under local anaesthesia, each patient was subjected to CT-guided sacroplasty using the long-axis approach through a single entry point. An average of 6 ml of polymethylmethacrylate (PMMA) was delivered along the path of each sacral fracture. For each individual patient, the Visual Analogue pain Scale (VAS) before sacroplasty and at 1, 4, 24 and 48 weeks after the procedure was obtained. Furthermore, the use of analgesics (narcotic/non-narcotic) along with the evolution of post-interventional patient mobility before and after sacroplasty was also recorded. The mean pre-procedure VAS was 8 ± 1.9 (range, 2 to 10). This rapidly and significantly (P < 0.001) declined in the first week after the procedure (mean 4 ± 1.4; range, 1 to 7) followed by a gradual and significant (P < 0.001) decrease along the rest of the follow-up period at 4 weeks (mean 3 ± 1.1; range, 1 to 5), 24 weeks (mean 2.2 ± 1.1; range, 1 to 5) and 48 weeks (mean 1.6 ± 1.1; range, 1 to 5). Eleven (58%) patients were under narcotic analgesia before sacroplasty, whereas 8 (42%) patients were using non-narcotics. Corresponding values after the procedure were 2/19 (10%; narcotic, one of them was on reserve) and 10/19 (53%; non-narcotic). The remaining 7 (37%) patients did not address post-procedure analgesic use. The evolution of post-interventional mobility was favourable in the study group as they revealed a significant improvement in their mobility point scale (P < 0.001). Long-axis percutaneous sacroplasty is a suitable, minimally invasive treatment option for patients who present with sacral insufficiency fractures. More studies with larger patient numbers are needed to explore any unrecognised limitations of this therapeutic approach.     

Recombinant carcinoembryonic antigen as a reporter gene for molecular imaging

Purpose  Reporter genes can provide a way of noninvasively assessing gene activity in vivo. However, current reporter gene strategies may be limited by the immunogenicity of foreign reporter proteins, endogenous expression, or unwanted biological activity. We have developed a reporter gene based on carcinoembryonic antigen (CEA), a human protein with limited normal tissue expression. Methods  To construct a CEA reporter gene for PET, a CEA minigene (N-A3) was fused to the extracellular and transmembrane domains of the human FcγRIIb receptor. The NA3-FcγRIIb recombinant gene, driven by a CMV promoter, was transfected in Jurkat (human T cell leukemia) cells. Expression was analyzed by flow cytometry, immunohistochemistry (IHC), and microPET imaging. Results  Flow cytometry identified Jurkat clones stably expressing NA3-FcγRIIb at low, medium, and high levels. High and medium NA3-FcγRIIb expression could also be detected by Western blot. Reporter gene positive and negative Jurkat cells were used to establish xenografts in athymic mice. IHC showed staining of the tumor with high reporter gene expression; medium and low N-A3 expression was not detected. MicroPET imaging, using an anti-CEA ¹²⁴I-labeled single-chain Fv-Fc antibody fragment, demonstrated that only high N-A3 expression could be detected. Specific accumulation of activity was visualized at the N-A3 positive tumor as early as 4 h. MicroPET image quantitation showed tumor activity of 1.8 ± 0.2, 15.2 ± 1.3, and 4.6 ± 1.2 percent injected dose per gram (%ID/g) at 4, 20, and 48 h, respectively. Biodistribution at 48 h demonstrated tumor uptake of 4.8 ± 0.8%ID/g. Conclusion  The CEA N-A3 minigene has the potential to be used as a reporter gene for imaging cells in vivo.     

Adequate image quality with reduced radiation dose in prospectively triggered coronary CTA compared with retrospective techniques

The goal of our study was to compare a prospective triggering (PT) CT technique with retrospectively gated (RG) CT techniques in coronary computed tomographic angiograms (CCTA) with respect to image quality and radiation dose. Sixty consecutive patients were enrolled. CCTAs using the RG technique were obtained with a dual-source 64-slice CT system in 40 patients, using ECG-triggered tube current modulation, with either a broad pulsing window at 30–80% of the RR interval (group RGb, 20 patients, heart rate > 70 bpm) or a small pulsing window at 70% (group RGs, 20 patients, heart rate < 70 bpm). The other 20 patients underwent CCTA using the PT technique on a 128-slice CT system (group PT, heart rate < 70 bpm). All images were evaluated by two observers for quality on a three-point scale, with 1 being excellent and 3 being insufficient. The effective radiation dose was calculated for each patient. The average image quality score was 1.5 ± 0.6 for PT, 1.35 ± 0.5 for RGs and 1.65 ± 0.5 for RGb. The mean effective dose for RGb was 9 ± 4 mSv, for RGs 7 ± 3 mSv and for PT 3 ± 1 mSv. This represents a 57% dose reduction for PT compared with RGs and a 67% dose reduction for PT compared with RGb. In conclusion, in selected patients CCTA with the PT technique offers adequate image quality with a significantly lower radiation dose compared with CCTA using RG techniques. None of the authors have financial or other kinds of interests that might pose a conflict of interest in connection with this article.     

Aperistaltic effect of hyoscine N-butylbromide versus glucagon on the small bowel assessed by magnetic resonance imaging

The aim of this prospective study was to compare the intraindividual aperistaltic effect of 40 mg hyoscine N-butylbromide (HBB/Buscopan) with that of 1 mg glucagon on small bowel motility by using magnetic resonance imaging (MRI). Ten healthy volunteers underwent two separate 1.5-T MRI studies (HBB/glucagon) after a standardized oral preparation with an aqueous solution of Gd-DOTA and ispaghula (Metamucil). A 2D T1-w GRE sequence was acquired (TR 2.7 ms/TE 1.3 ms, temporal resolution 0.25 s) before and after intravenous (i.v.) drug administration and motility was followed over 1 h. On the resulting images the cross-sectional luminal diameters were assessed and plotted over time. Baseline motility frequency, onset of aperistalsis, duration of arrest, reappearance of motility and return to normal motility were analysed. Significant differences regarding reliability and duration of aperistalsis were observed. In the HBB group aperistalsis lasted a mean of 6.8 ± 5.3 min compared with 18.3 ± 7 min after glucagon (p < 0.0001). In 50% of cases HBB did not accomplish aperistalsis, whereas glucagon always succeeded (p = 0.05). There were no significant differences in terms of baseline and end frequencies for the onset of aperistalsis (22.2 ± 37.5 s HBB/13.4 ± 9.2 s glucagon, p = 0.1), nor for the return to normal motility. Arrest of small bowel motion is achieved more reliably and lasts significantly longer after i.v. administration of 1 mg glucagon compared with 40 mg HBB.     

Three-dimensional Monte Carlo-based voxel-wise tumor dosimetry in patients with neuroendocrine tumors who underwent 177 Lu-DOTATOC therapy

Patients with advanced neuroendocrine tumors (NETs) of the midgut are suitable candidates for 177Lu-DOTATOC therapy. Integrated SPECT/CT systems have the potential to help improve the accuracy of patient-specific tumor dosimetry. Dose estimations to target organs are generally performed using the Medical Internal Radiation Dose scheme. We present a novel Monte Carlo-based voxel-wise dosimetry approach to determine organ- and tumor-specific total tumor doses (TTD). A cohort of 14 patients with histologically confirmed metastasized NETs of the midgut (11 men, 3 women, 62.3 ± 11.0 years of age) underwent a total of 39 cycles of 177Lu-DOTATOC therapy (mean 2.8 cycles, SD ± 1 cycle). After the first cycle of therapy, regions of interest were defined manually on the SPECT/CT images for the kidneys, the spleen, and all 198 tracer-positive tumor lesions in the field of view. Four SPECT images, taken at 4 h, 24 h, 48 h and 72 h after injection of the radiopharmaceutical, were used to determine their effective half-lives in the structures of interest. The absorbed doses were calculated by a three-dimensional dosimetry method based on Monte Carlo simulations. TTD was calculated as the sum of all products of single tumor doses with single tumor volumes divided by the sum of all tumor volumes. The average dose values per cycle were 3.41 ± 1.28 Gy (1.91–6.22 Gy) for the kidneys, 4.40 ± 2.90 Gy (1.14–11.22 Gy) for the spleen, and 9.70 ± 8.96 Gy (1.47–39.49 Gy) for all 177Lu-DOTATOC-positive tumor lesions. Low- and intermediate-grade tumors (G 1–2) absorbed a higher TTD compared to high-grade tumors (G 3) (signed-rank test, p =  < 0.05). The pre-therapeutic chromogranin A (CgA) value and the TTD correlated significantly (Pearson correlation:  = 0.67, p = 0.01). Higher TTD resulted in a significant decrease of CgA after therapy. These results suggest that Monte Carlo-based voxel-wise dosimetry is a very promising tool for predicting the absorbed TTD based on histological and clinical parameters.     

Peri-ictal signal changes in seven patients with status epilepticus: interesting MRI observations

Introduction  Transient peri-ictal changes on imaging had been described following status epilepticus (SE), but its cause is not very well understood. We analyzed the magnetic resonance imaging (MRI) findings in SE patients in order to elucidate such changes including peri-ictal signal. Materials and methods  This prospective study involved 34 patients (M/F 23:11, mean age 25.8 ± 17.2 years) who experienced SE. MRI was performed during or within 96 h of cessation of seizures. Twenty-five patients had generalized convulsive status epilectus (GCSE; ten secondary GCSE and 15 primary GCSE). Seven patients had epilepsia partialis continua and two patients non-convulsive SE. Eight patients had a history of seizures and three patients previous SE. The mean duration of SE prior to MRI was 89.2 ± 105.3 h (range 2–360 h). MRI provided diagnosis in 17 patients, and in 13 patients, no structural cause was identified. Results  Peri-ictal focal signal changes with restricted diffusion on apparent diffusion coefficient maps were present in seven (20.6%) patients with SE (generalized convulsive, three; partial, three; non-convulsive, one). The changes were observed when MRI was performed during SE in 3/10 (30%) patients, or within 24 h in 1/7 (14.3%), 48 h in 1/5 (20%), 72 h in 1/6 (16.7%), or 96 h in 1/6 (16.7%) patients after cessation of seizures. Repeat MRI revealed disappearance of signal changes in two patients. Conclusions  Peri-ictal MR changes with restricted diffusion appear to be an effect rather than the cause of SE.     

Prevalence and morphology of coronary artery ectasia with dual-source CT coronary angiography

To assess the prevalence and morphological characteristics of coronary artery ectasia (CAE) with CT coronary angiography (CTCA) in comparison to conventional catheterangiography (CCA). Dual-source CTCA examinations from 677 consecutive patients (223 women; median age 57 years) were retrospectively evaluated by two blinded observers for the presence of CAE defined as a diameter enlargement ≥1.5 times the diameter of adjacent normal coronary segments. Vessel diameters and contrast attenuation within and proximal to ectatic segments were measured. CCA was used to compare measurements obtained from CTCA with the coronary flow velocity by using the thrombolysis in myocardial infarction (TIMI) frame count. CTCA identified CAE in 20 of 677 (3%) patients. CCA was performed in ten of these patients. CAE diameter measurements with CTCA (10.0 ± 5.4 mm) correlated significantly (r = 0.92, p < 0.001) with the CCA measurements (8.8 ± 4.9 mm), but had higher diameters (levels of agreement: −1.0 to 3.4 mm). Contrast attenuation was significantly lower in the ectatic (343 ± 63 HU) than in the proximal (394 ± 60 HU) segments (p < 0.01). The attenuation difference significantly correlated with the CAE ratio (r = 0.67, p < 0.01) and the TIMI frame count (r = 0.58, p < 0.05). The prevalence of CAE in a population examined by CTCA is around 3%. Contrast attenuation measurements with CTCA correlate well with the flow alterations assessed with CCA.     

Prediction of functional recovery after revascularization using quantitative gated myocardial perfusion SPECT: a multi-center cohort study in Japan

Backgrounds  Prediction of left ventricular functional recovery is important after myocardial infarction. The impact of quantitative perfusion and motion analyses with gated single-photon emission computed tomography (SPECT) on predictive ability has not been clearly defined in multi-center studies. Methods  A total of 252 patients with recent myocardial infarction (n = 74) and old myocardial infarction (n = 175) were registered from 25 institutions. All patients underwent resting gated SPECT using ^99mTc-hexakis-2-methoxy-isobutyl isonitrile (MIBI) and repeated the study after revascularization after an average follow-up period of 132 ± 81 days. Visual and quantitative assessment of perfusion and wall motion were performed in 5,040 segments. Results  Non-gated segmental percent uptake and end-systolic (ES) percent uptake were good predictors of wall motion recovery and significantly differed between improved and non-improved groups (66 ± 17% and 55 ± 18%, p < 0.0001 for non-gated; 64 ± 16% and 51 ± 17% for ES percent uptake, p < 0.0001). The area under the curve of receiver operating characteristics curve for non-gated percent uptake, ES percent uptake, end-diastolic percent uptake and visual perfusion defect score was 0.70, 0.71, 0.61, and 0.56, respectively. Sensitivity and specificity of percent uptake were 68% and 64% for non-gated map and 80% and 52% for ES percent uptake map. An optimal threshold for predicting segmental improvement was 63% for non-gated and 52% for ES percent uptake values. Conclusion  Segmental ^99mTc-MIBI uptake provided a useful predictor of wall motion improvement. Application of quantitative approach with non-gated and ES percent uptake enhanced predictive accuracy over visual analysis particularly in a multi-center study.     

Follow-up of pain processing recovery after ketamine in hyperalgesic fibromyalgia patients using brain perfusion ECD-SPECT

Purpose The aim of this study was to determine whether the follow-up of pain processing recovery in hyperalgesic fibromyalgia (FM) could be objectively evaluated with brain perfusion ethyl cysteinate dimer single photon computerized tomography (ECD-SPECT) after administration of ketamine. Materials and methods We enrolled 17 hyperalgesic FM women patients (48.5 ± 11 years, range 25–63). After treatment with subcutaneous ketamine, 11 patients were considered as “good responders”, with a decrease in pain intensity, evaluated by visual analog scale (VAS), greater than 50%. On the other hand, six patients were considered as “poor responders”. A voxel-based analysis of regional cerebral blood flow (rCBF) was conducted (p _voxel < 0.001uc), in the two subgroups of patients, before and after treatment, in comparison to a group of ten healthy subjects, matched for age and gender. Results In comparison to baseline brain SPECT, midbrain rCBF showed a greater increase after ketamine in the responder group than in the nonresponder group (p _cluster = 0.016c). In agreement with the clinical response, the change in midbrain rCBF after ketamine was highly correlated with the reduction of VAS pain score (r = 0.7182; p = 0.0041). Conclusion This prospective study suggests that blockade of facilitatory descending modulation of pain with ketamine can be evaluated in the periaqueductal grey with brain perfusion SPECT.     

Dual-modality optical and positron emission tomography imaging of vascular endothelial growth factor receptor on tumor vasculature using quantum dots

Purpose  To date, the in vivo imaging of quantum dots (QDs) has been mostly qualitative or semiquantitative. The development of a dual-function positron emission tomography (PET)/near-infrared fluorescence (NIRF) probe might allow the accurate assessment of the tumor-targeting efficacy of QDs. Materials and methods  An amine-functionalized QD was conjugated with VEGF protein and DOTA chelator for VEGFR-targeted PET/NIRF imaging after ⁶⁴Cu-labeling. The targeting efficacy of this dual functional probe was evaluated in vitro and in vivo through cell-binding assay, cell staining, in vivo optical/PET imaging, ex vivo optical/PET imaging, and histology. Results  The DOTA–QD–VEGF exhibited VEGFR-specific binding in both cell-binding assay and cell staining experiment. Both NIR fluorescence imaging and microPET showed VEGFR-specific delivery of conjugated DOTA–QD–VEGF nanoparticle and prominent reticuloendothelial system uptake. The U87MG tumor uptake of ⁶⁴Cu-labeled DOTA–QD was less than one percentage injected dose per gram (%ID/g), significantly lower than that of ⁶⁴Cu-labeled DOTA–QD–VEGF (1.52 ± 0.6%ID/g, 2.81 ± 0.3%ID/g, 3.84 ± 0.4%ID/g, and 4.16 ± 0.5%ID/g at 1, 4, 16, and 24 h post injection, respectively; n = 3). Good correlation was also observed between the results measured by ex vivo PET and NIRF organ imaging. Histologic examination revealed that DOTA–QD–VEGF primarily targets the tumor vasculature through a VEGF–VEGFR interaction. Conclusion  We have successfully developed a QD-based nanoprobe for dual PET and NIRF imaging of tumor VEGFR expression. The success of this bifunctional imaging approach may render higher degree of accuracy for the quantitative targeted NIRF imaging in deep tissue.     

Detection and characteristics of microvascular obstruction in reperfused acute myocardial infarction using an optimized protocol for contrast-enhanced cardiovascular magnetic resonance imaging

Several cardiovascular magnetic resonance imaging (CMR) techniques are used to detect microvascular obstruction (MVO) after acute myocardial infarction (AMI). To determine the prevalence of MVO and gain more insight into the dynamic changes in appearance of MVO, we studied 84 consecutive patients with a reperfused AMI on average 5 and 104 days after admission, using an optimised single breath-hold 3D inversion recovery gradient echo pulse sequence (IR-GRE) protocol. Early MVO (2 min post-contrast) was detected in 53 patients (63%) and late MVO (10 min post-contrast) in 45 patients (54%; p = 0.008). The extent of MVO decreased from early to late imaging (4.3 ± 3.2% vs. 1.8 ± 1.8%, p < 0.001) and showed a heterogeneous pattern. At baseline, patients without MVO (early and late) had a higher left ventricular ejection fraction (LVEF) than patients with persistent late MVO (56 ± 7% vs. 48 ± 7%, p < 0.001) and LVEF was intermediate in patients with early MVO but late MVO disappearance (54 ± 6%). During follow-up, LVEF improved in all three subgroups but remained intermediate in patients with late MVO disappearance. This optimised single breath-hold 3D IR-GRE technique for imaging MVO early and late after contrast administration is fast, accurate and allows detection of patients with intermediate remodelling at follow-up.     

Comprehensive evaluation of occupational radiation exposure to intraoperative and perioperative personnel from <Superscript>18</Superscript>F-FDG radioguided surgical procedures

Purpose  The purpose of the current study was to comprehensively evaluate occupational radiation exposure to all intraoperative and perioperative personnel involved in radioguided surgical procedures utilizing ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). Methods  Radiation exposure to surgeon, anesthetist, scrub technologist, circulating nurse, preoperative nurse, and postoperative nurse, using aluminum oxide dosimeters read by optically stimulated luminescence technology, was evaluated during ten actual radioguided surgical procedures involving administration of ¹⁸F-FDG. Results  Mean patient dosage of ¹⁸F-FDG was 699 ± 181 MBq (range 451–984). Mean time from ¹⁸F-FDG injection to initial exposure of personnel to the patient was shortest for the preoperative nurse (75 ± 63 min, range 0–182) followed by the circulating nurse, anesthetist, scrub technologist, surgeon, and postoperative nurse. Mean total time of exposure of the personnel to the patient was longest for the anesthetist (250 ± 128 min, range 69–492) followed by the circulating nurse, scrub technologist, surgeon, postoperative nurse, and preoperative nurse. Largest deep dose equivalent per case was received by the surgeon (164 ± 135 μSv, range 10–580) followed by the anesthetist, scrub technologist, postoperative nurse, circulating nurse, and preoperative nurse. Largest deep dose equivalent per hour of exposure was received by the preoperative nurse (83 ± 134 μSv/h, range 0–400) followed by the surgeon, anesthetist, postoperative nurse, scrub technologist, and circulating nurse. Conclusion  On a per case basis, occupational radiation exposure to intraoperative and perioperative personnel involved in ¹⁸F-FDG radioguided surgical procedures is relatively small. Development of guidelines for monitoring occupational radiation exposure in ¹⁸F-FDG cases will provide reassurance and afford a safe work environment for such personnel.     

Kinetics in serum and urinary excretion of ethyl sulfate and ethyl glucuronide after medium dose ethanol intake

The direct ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), are of increasing importance for clinical and forensic applications, but there are only few studies on the kinetics of EtG in serum and none on EtS. In this study, 13 volunteers (social drinkers) drank ethanol in the form of white wine to reach a blood alcohol concentration of 0.51 ± 0.17 g/kg, and blood and urine samples were analyzed for EtG and EtS simultaneously by chromatography-tandem mass spectrometry (LC-MS/MS). Mean peak serum EtG and EtS concentrations were 2.9 ± 1.3 and 2.8 ± 1.6 μmol/l, respectively, and were reached between 4.0 ± 0.9 h after the start of drinking (3.0 ± 0.5 h for EtS). The mean time differences between reaching maximum blood ethanol levels and serum metabolite levels were 2.3 ± 0.9 h for EtG and 1.2 ± 0.5 h for EtS. In the last blood samples collected (10–11 h after the start of drinking), 11 (of 13) volunteers were still positive for EtG in serum, whereas only 2 were positive for EtS. In the serum of one female person, no EtS was detectable at any time; however, it was excreted in the urine in (low) concentrations. Ethanol was detectable in the serum for up to 8.6 h after the start of drinking, whereas EtG and EtS were detectable up to more than 5.8 h (EtG) and 4.0 h (EtS), respectively. Mean peak urinary concentrations were 401 ± 232 μmol/l for EtG and 266 ± 153 μmol/l for EtS, and mean peak levels were reached 6.2 ± 0.9 h (EtG) and 5.3 ± 1.2 h (EtS) after the start of drinking. Maximum concentrations of EtG and EtS in serum showed a wide interindividual variation and could not be correlated to the maximum blood ethanol concentrations. Correlations (p < 0.001, Kendall’s Tau b) were found when comparing pairs of parameters, but mostly involved areas under the curve (AUC) of metabolites or of ethanol; one correlation linked the peak concentrations of EtG and EtS in urine. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Absolute choline concentration measured by quantitative proton MR spectroscopy correlates with cell density in meningioma

Introduction  This study was aimed to investigate the relationship between quantitative proton magnetic resonance spectroscopy (1H-MRS) and pathological changes in meningioma. Materials and methods  Twenty-two meningioma cases underwent single voxel 1H-MRS (point-resolved spectroscopy sequence, repetition time/echo time = 2,000 ms/68, 136, 272 ms). Absolute choline (Cho) concentration was calculated using tissue water as the internal reference and corrected according to intra-voxel cystic/necrotic parts. Pathological specimens were stained with MIB-1 antibody to measure cell density and proliferation index. Correlation analysis was performed between absolute Cho concentration and cell density and MIB-1 labeled proliferation index. Results  Average Cho concentration of all meningiomas before correction was 2.95 ± 0.86 mmol/kg wet weight. It was increased to 3.23 ± 1.15 mmol/kg wet weight after correction. Average cell density of all meningiomas was 333 ± 119 cells/HPF, and average proliferation index was 2.93 ± 5.72%. A linear, positive correlation between cell density and Cho concentration was observed (r = 0.650, P = 0.001). After correction of Cho concentration, the correlation became more significant (r = 0.737, P < 0.001). However, no significant correlation between Cho concentration and proliferation index was found. There seemed to be a positive correlation trend after correction of Cho concentration but did not reach significant level. Conclusion  Absolute Cho concentration, especially Cho concentration corrected according to intra-voxel cystic/necrotic parts, reflects cell density of meningioma. Grant: This study was supported by the Japan-China Sasakawa Medical Fellowship (Nippon Foundation, Japan)     

Oral administration of choline does not affect metabolic characteristics of gliomas and normal-appearing white matter, as detected with single-voxel 1H-MRS at 1.5 T

Introduction  The present study was done for evaluation of the possible influence of the oral administration of choline on metabolic characteristics of gliomas detected with proton magnetic resonance spectroscopy (¹H-MRS). Materials and methods  Thirty patients (22 men and eight women; mean age 38 ± 15 years) with suspicious intracranial gliomas underwent single-voxel long-echo (TR 2,000 ms, TE 136 ms, 128–256 acquisitions) ¹H-MRS of the tumor, peritumoral brain tissue, and distant normal-appearing white matter before and several hours (median, 3 h; range, 1.2–3.7 h) after ingestion of choline with prescribed dose of 50 mg/kg (median actual dose, 52 mg/kg; range, 48–78 mg/kg). Investigations were done using 1.5 T clinical magnetic resonance imager. The volume of the rectangular ¹H-MRS voxel was either 3.4 or 8 cm³. At the time of both spectroscopic examinations, similar voxels’ positioning and size and technical parameters of ¹H-MRS were used. Surgery was done in 27 patients within 1 to 68 days thereafter. In all cases, more than 80% resection of the neoplasm was attained. Results  There were 12 low-grade gliomas and 15 high-grade gliomas. MIB-1 index varied from 0% to 51.7% (median, 13.8%). Statistical analysis did not disclose significant differences of any investigated metabolic parameter of the tumor, peritumoral brain tissue and distant normal-appearing white matter between two spectroscopic examinations. Conclusion  Single-voxel ¹H-MRS at 1.5 T could not detect significant changes of the metabolic characteristics of gliomas, peritumoral brain tissue, and distant normal-appearing white matter after oral administration of choline.