Study of Vesicular Monoamine Transporter 2 in Myopic Retina Using [<Superscript>18</Superscript>F]FP-(+)-DTBZ

Purpose

To investigate the relationship between expression level of vesicular monoamine transporter 2 (VMAT2) and myopia, as well as the feasibility of noninvasive myopia diagnosis through imaging VMAT2 in retina by using [¹⁸F]fluoropropyl-(+)-dihydrotetrabenazine ([¹⁸F]FP-(+)-DTBZ).

Procedures

The right eyes of ten guinea pigs were deprived of vision to establish form-deprived (FD) myopia and the left eyes were untreated as the self-control eyes. The location and expression level of VMAT2 in the eyes were detected by micro-positron emission tomography (PET)/X-ray computed tomography (CT) imaging through using [¹⁸F]FP-(+)-DTBZ. Immunofluorescence staining and Western blot were used to confirm the location and expression level of VMAT2 in the eyes. The concentrations of dopamine (DA) and its metabolites including 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were also investigated by high-performance liquid chromatography.

Results

The right eyes deprived of vision were obviously myopic (??3.17?±?1.33 D) after procedure, while the left eyes were hyperopic (4.60?±?0.83 D, P?<?0.0001). The main expressions of VMAT2 in the eyes were located in retina. VMAT2 was significantly reduced in the myopic retina compared to the normal one from PET/CT results (P?=?0.0008), which could also be verified by Western blots (P?=?0.029). The concentrations of DA, DOPAC, and HVA in the FD eyes were all significantly less than those in the control eyes (P?=?0.024, P?=?0.018, P?=?0.008). As a role of storing and releasing DA in vesicles, VMAT2 was demonstrated positively correlating with the amounts of DA (P?=?0.030), DOPAC (P?=?0.038), and HVA (P?=?0.025) through Pearson’s correlation coefficient test.

Conclusions

We demonstrate that [¹⁸F]FP-(+)-DTBZ can be used to noninvasively image VMAT2 in retina. The expression level of VMAT2 in retina may act as a new biomarker for myopia diagnosis. The decreasing of VMAT2 expression level may play an important role in the development of myopia through correspondingly reducing the amount of DA in retina.

     

Comparison of [<Superscript>11</Superscript>C]Choline ([<Superscript>11</Superscript>C]CHO) and [<Superscript>18</Superscript>F]Bombesin (BAY 86-4367) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model

Purpose

Carbon-11- and fluorine-18-labeled choline derivatives are commonly used in prostate cancer imaging in the clinical setting for staging and re-staging of prostate cancer. Due to a limited detection rate of established positron emission tomography (PET) tracers, there is a clinical need for innovative tumor-specific PET compounds addressing new imaging targets. The aim of this study was to compare the properties of [¹⁸F]Bombesin (BAY 86-4367) as an innovative biomarker for prostate cancer imaging targeting the gastrin-releasing peptide receptor and [¹¹C]Choline ([¹¹C]CHO) in a human prostate tumor mouse xenograft model by small animal PET/X-ray computed tomography (CT).

Procedures

We carried out a dual-tracer small animal PET/CT study comparing [¹⁸F]Bombesin and [¹¹C]CHO. The androgen-independent human prostate tumor cell line PC-3 was implanted subcutaneously in the flanks of nu/nu NMRI mice (n?=?10) (PET/CT measurements of two [¹¹C]Choline mice could not be analyzed due to technical reasons). [¹⁸F]Bombesin and [¹¹C]CHO PET/CT imaging was performed about 3–4 weeks after the implantation of PC-3 cells on two separate days. After the intravenous tail vein injection of 14 MBq [¹⁸F]Bombesin and 37 MBq [¹¹C]CHO, respectively, a dynamic study over 60 min was acquired in list mode using an Inveon animal PET/CT scanner (Siemens Medical Solutions). The sequence of [¹⁸F]Bombesin and [¹¹C]CHO was randomized. Image analysis was performed using summed images as well as dynamic data. To calculate static and dynamic tumor-to-muscle (T/M), tumor-to-blood (T/B), liver-to-blood (L/B), and kidney-to-blood (K/B) ratios, 4?×?4?×?4 mm³ volumes of interest (VOIs) of tumor, muscle (thigh), liver, kidney, and blood derived from transversal slices were used.

Results

The mean T/M ratio of [¹⁸F]Bombesin and [¹¹C]CHO was 6.54?±?2.49 and 1.35?±?0.30, respectively. The mean T/B ratio was 1.83?±?0.79 for [¹⁸F]Bombesin and 0.55?±?0.10 for [¹¹C]CHO. The T/M ratio as well as the T/B ratio for [¹⁸F]Bombesin were significantly higher compared to those for [¹¹C]CHO (p?<?0.001, respectively). Kidney and liver uptake was statistically significantly lower for [¹⁸F]Bombesin (K/B 3.41?±?0.81, L/B 1.99?±?0.38) compared to [¹¹C]CHO [K/B 7.91?±?1.85 (p?<?0.001), L/B 6.27?±?1.99 (p?<?0.001)]. The magnitudes of the time course of T/M and T/B ratios (T/M and T/B_dyn ratios) were statistically significantly different (showing a higher uptake of [¹⁸F]Bombesin compared to [¹¹C]CHO); additionally, also the change of the T/M and T/B ratios over time was significantly different between both tracers in the dynamic analysis (p?<?0.001, respectively). Furthermore, there was a statistically significantly different change of the K/B and L/B ratios over time between the two tracers in the dynamic analysis (p?=?0.026 and p?<?0.001, respectively).

Conclusions

[¹⁸F]Bombesin (BAY 86-4367) visually and semi-quantitatively outperforms [¹¹C]CHO in the PC-3 prostate cancer xenograft model. [¹⁸F]Bombesin tumor uptake was significantly higher compared to [¹¹C]CHO. [¹⁸F]Bombesin showed better imaging properties compared to the clinically utilized [¹¹C]CHO due to a higher tumor uptake as well as a lower liver and kidney uptake.

     

Differences between first-generation and second-generation drug-eluting stent regarding in-stent neoatherosclerosis characteristics: an optical coherence tomography analysis

We compared first-generation and second-generation drug-eluting stent (DES) with respect to neoatherosclerosis using optical coherence tomography or optical frequency domain imaging. In-stent restenoses in 102 first-generation and 114 second-generation DES were retrospectively assessed. Neoatherosclerosis, which was defined as the presence of lipid-laden neointima or calcification inside a stent, was observed in 33 (27.2%) and 31 (32.4%) lesions in the first-generation and second-generation DES respectively. In the first-generation DES group, the lipid length was significantly longer (5.5?±?3.8 vs. 3.1?±?2.1 mm, P?=?0.0007), the lipid arc was significantly larger (324?±?70° vs. 250?±?94°, P?=?0.002), the prevalence of a 360° lipid arc was significantly greater (58 vs. 31%, P?=?0.03), and the fibrous cap was significantly thinner (153?±?85 vs. 211?±?95 µm, P?=?0.02) compared with those in the second-generation DES group. These differences remained significant after adjusting for the age of the stent (lipid length: P?<?0.001; lipid arc: P?=?0.019; and fibrous cap thickness: P?<?0.001). The proliferation course and stability of neoatherosclerosis over time might be superior in second-generation DES.     

Predictive Value of Asphericity in Pretherapeutic [<Superscript>111</Superscript>In]DTPA-Octreotide SPECT/CT for Response to Peptide Receptor Radionuclide Therapy with [<Superscript>177</Superscript>Lu]DOTATATE

Purpose

The purpose of this study was to assess the value of the spatial heterogeneity of somatostatin receptor (SSR) volume, quantified as asphericity (ASP), and to predict response to peptide receptor radionuclide therapy (PRRT) in patients with metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN).

Procedures

From June 2011 to May 2013, patients suffering from GEP-NEN who underwent pretherapeutic [¹¹¹In-DTPA⁰]octreotide scintigraphy (Octreoscan®) prior to [¹⁷⁷Lu-DOTA⁰-Tyr³]octreotate ([¹⁷⁷Lu]DOTATATE)-PRRT were enrolled in this retrospective evaluation. SSR expression in 20 NEN patients was qualitatively and quantitatively assessed using the Krenning score, the metastasis to liver uptake ratio (M/L ratio), and ASP at baseline. Response to PRRT was evaluated based on lesions, which were classified as responding lesions (RL) and non-responding lesions (NRL) after 4- and 12-month follow-ups. The values of the Krenning score, M/L ratio, and ASP for response prediction were compared by using the Mann-Whitney U test, Kruskal-Wallis test, and receiver operating characteristic (ROC) curves.

Results

Seventy-seven metastases (liver, n = 40; lymph node, n = 24; bone, n = 11; pancreas, n = 2) showed SSR expression. A higher ASP level was significantly associated with poorer response at both time points. ROC analyses revealed the highest area under the curve (AUC) for discrimination between RL and NRL for ASP after 4 months (AUC 0.97; p = 0.019) and after 12 months (AUC 0.96; p < 0.001), followed by the Krenning score (AUC 0.74; p = 0.082 and AUC 0.85; p < 0.001, respectively) and M/L ratio (AUC 0.77; p = 0.107 and AUC 0.82; p < 0.001). The optimal cutoff value for ASP was 5.12 % (sensitivity, 90 %; specificity, 93 %).

Conclusion

Asphericity of SSR-expressing lesions in pretherapeutic single-photon emission computed tomography with integrated computed tomography (SPECT/CT) is a promising parameter for predicting response to PRRT in gastroenteropancreatic neuroendocrine neoplasms.

     

Dynamic changes in injured myocardium,very early after acute myocardial infarction,quantified using T1 mapping cardiovascular magnetic resonance

Background

It has recently been suggested that myocardial oedema follows a bimodal pattern early post ST-segment elevation myocardial infarction (STEMI). Yet, water content, quantified using tissue desiccation, did not return to normal values unlike oedema quantified by cardiovascular magnetic resonance (CMR) imaging. We studied the temporal changes in the extent and intensity of injured myocardium using T1-mapping technique within the first week after STEMI.

Methods

A first group (n?=?31) underwent 3 acute 3?T CMR scans (time-point (TP) <?3?h, 24?h and 6?days), including cine, native shortened modified look-locker inversion recovery T1 mapping, T2* mapping and late gadolinium enhancement (LGE). A second group (n?=?17) had a single scan at 24?h with an additional T2-weighted sequence to assess the difference in the extent of area-at-risk (AAR) compared to T1-mapping.

Results

The mean T1 relaxation time value within the AAR of the first group was reduced after 24?h (P?<?0.001 for TP1 vs.TP2) and subsequently increased at 6?days (P?=?0.041 for TP2 vs.TP3). However, the extent of AAR quantified using T1-mapping did not follow the same course, and no change was detected between TP1&TP2 (P?=?1.0) but was between TP2 &TP3 (P?=?0.019). In the second group, the extent of AAR was significantly larger on T1-mapping compared to T2-weighted (42?±?15% vs. 39?±?15%, P?=?0.025). No change in LGE was detected while microvascular obstruction and intra-myocardial haemorrhage peaked at different time points within the first week of reperfusion.

Conclusion

The intensity of oedema post-STEMI followed a bimodal pattern; while the extent of AAR did not track the same course. This discrepancy has implications for use of CMR in this context and may explain the previously reported disagreement between oedema quantified by imaging and tissue desiccation.

     

Phase 1 Evaluation of [<Superscript>64</Superscript>Cu]DOTA-Patritumab to Assess Dosimetry,Apparent Receptor Occupancy,and Safety in Subjects with Advanced Solid Tumors

Purpose

The purpose of this study was to evaluate the safety, dosimetry, and apparent receptor occupancy (RO) of [⁶⁴Cu]DOTA-patritumab, a radiolabeled monoclonal antibody directed against HER3/ERBB3 in subjects with advanced solid tumors.

Procedures

Dosimetry subjects (n?=?5) received [⁶⁴Cu]DOTA-patritumab and underwent positron emission tomography (PET)/X-ray computed tomography (CT) at 3, 24, and 48 h. Evaluable RO subjects (n?=?3 out of 6) received [⁶⁴Cu]DOTA-patritumab at day 1 and day 8 (after 9.0 mg/kg patritumab) followed by PET/CT at 24 h post-injection. Endpoints included safety, tumor uptake, and efficacy.

Results

The tumor SUV_max (±?SD) was 5.6?±?4.5, 3.3?±?1.7, and 3.0?±?1.1 at 3, 24, and 48 h in dosimetry subjects. The effective dose and critical organ dose (liver) averaged 0.044?±?0.008 mSv/MBq and 0.46?±?0.086 mGy/MBq, respectively. In RO subjects, tumor-to-blood ratio decreased from 1.00?±?0.32 at baseline to 0.57?±?0.17 after stable patritumab, corresponding to a RO of 42.1?±?3.

Conclusions

[⁶⁴Cu]DOTA-patritumab was safe. These limited results suggest that this PET-based method can be used to determine tumor-apparent RO.

     

Acceleration of the learning curve for mastering basic critical care echocardiography using computerized simulation

Purpose

To assess the impact of computerized transthoracic echocardiography (TTE) simulation on the learning curve to achieve competency in basic critical care echocardiography (CCE).

Methods

In this prospective bicenter study, noncardiologist residents novice in ultrasound followed either a previously validated training program with adjunctive computerized simulation on a mannequin (two 3 h-sessions; Vimedix simulator, CAE Healthcare) (interventional group; n?=?12) or solely the same training program (control group; n?=?12). All trainees from the same institution were assigned to the same study group to avoid confusion bias. Each trainee was evaluated after 1 (M1), 3 (M3) and 6 (M6) months of training using our previously validated scoring system. Competency was defined by a score?≥?90% of the maximal value.

Results

The 24 trainees performed 965 TTE in patients with cardiopulmonary compromise during their 6-month rotation. Skills assessments relied on 156 TTE performed in 106 patients (mean age 53?±?14 years; mean Simplified Acute Physiologic Score 2: 55?±?19; 79% ventilated). When compared to the control group, trainees of the interventional group obtained a significantly higher mean skills assessment score at M1 (41.5?±?4.9 vs. 32.3?±?3.7: P?=?0.0004) and M3 (45.8?±?2.8 vs. 42.3?±?3.7: P?=?0.0223), but not at M6 (49.7?±?1.2 vs. 50.0?±?2.7: P?=?0.6410), due to higher practical and technical skills scores. Trainees of the control group required significantly more supervised TTE to obtain competency than their counterparts (36?±?7 vs. 30?±?9: p?=?0.0145).

Conclusions

Adjunctive computerized simulation accelerates the learning curve of basic CCE in improving practical and technical skills and reduces the number of TTE examinations required to reach competency.

     

Improved Differentiation of Low-Grade and High-Grade Gliomas and Detection of Tumor Proliferation Using APT Contrast Fitted from Z-Spectrum

Purpose

The purpose of the study is to demonstrate the value of quantitative amide proton transfer (APT) imaging for differentiating glioma grades and detecting tumor proliferation.

Procedures

This study included 32 subjects with 16 low-grade gliomas (LGG) and 16 high-grade gliomas (HGG) confirmed by histopathology. Chemical exchange saturation transfer (CEST) magnetic resonance imaging with APT weighting was performed on a 3 T scanner. After B₀ correction, Z-spectra were fitted with Lorentzian functions corresponding to the upfield semi-solid magnetization transfer and nuclear overhauser enhancement (MT&NOE) effect, the direct saturation (DS) effect, and the downfield APT effect centered at around ??1.5, 0, and +?3.5 ppm, respectively. To compute the Z-spectral fitted APT (fitted_APT) in solid tumor tissue, double-peak histogram fitting of pixel MT&NOE effect from the whole tumor was used to remove necrosis regions. The fitted APT was then compared with the conventional APT based on magnetization transfer ratio asymmetry. Receiver operating characteristic (ROC) analysis was used to compare the performance between Z-spectral fitted contrasts and the con_APT for LGG versus HGG differentiation. Additionally, the correlations between the imaging contrasts (fitted_APT, con_APT, and fitted_MT&NOE) and Ki-67 labeling index for tumor proliferation were also evaluated.

Results

Z-spectral fitted_APT shows improved statistical power for differentiating HGG and LGG (7.58?±?0.99 vs. 6.79?±?1.05 %, p?<?0.05) than con_APT (4.34?±?0.95 vs. 4.05?±?2.02 %, p?>?0.05) in solid tumor tissues. Analyses of whole tumor, on the other hand, have less differentiating power for both fitted_APT (p from 0.032 to 0.08) and con_APT (p from 0.696 to 0.809). Similarly, based on ROC analyses, fitted_APT shows larger area under the curve (AUC?=?0.723) than con_APT (AUC?=?0.543). The combination of fitted APT, DS, and MT&NOE further improved the specificity (75 %), diagnostic accuracy (78.2 %), and area under the curve (0.758) in differentiating LGG and HGG. Consistently, fitted_APT (r?=?0.451, p?=?0.018) is better correlated with Ki-67 than con_APT (r?=?0.331, p?=?0.092).

Conclusions

Fitted APT from Z-spectrum improves differentiation of low- and high-grade gliomas and better correlated with tumor proliferation than conventional APT.

     

Biodistribution of [<Superscript>68</Superscript>Ga]PSMA-HBED-CC in Patients with Prostate Cancer: Characterization of Uptake in Normal Organs and Tumour Lesions

Purpose

The aim of this study was to determine the physiological and pathophysiological biodistribution of [⁶⁸Ga]PSMA-HBED-CC (PSMA-11) ([⁶⁸Ga]PSMA) in patients with prostate cancer (PCA) to establish the range of normal uptake in relevant organs and primary prostate tumours, locally recurrent PCA, lymph and bone metastases and other metastatic lesions. Additionally, we aimed to determine a cut-off uptake value for differentiation of primary tumours from normal prostate tissue.

Procedures

Overall, [⁶⁸Ga]PSMA positron emission tomography/x-ray computed tomography (PET/CT) of 101 patients (mean age 69.1 years) with PCA was analysed retrospectively. For assessment of tracer biodistribution, maximum standardized uptake values (SUVmax) were calculated for various normal organs, as well as for primary tumours (PT) and/or metastases. Results are presented as median, interquartile range (IQR; 25th quantil–75th quantil) and range (minimum–maximum).

Results

[⁶⁸Ga]PSMA PET/CT was performed 50 min (range 30–126) after injection of 109 MBq (range 84–158). Regarding biodistribution, highest uptake (median/IQR/range) of the tracer was found in the kidneys (49.6/40.7–57.6/2.7–97.0) followed by the submandibular glands (17.3/13.7–21.2/7.5–30.4), parotid glands (16.1/12.2–19.8/5.5–30.9) and duodenum (13.8/10.5–17.2/5.8–26.9). The best cut-off value for differentiating physiological uptake in the primary tumour from that in the prostate was found to be an SUVmax of 3.2. The median SUVmax in the PT (n?=?35), locally recurrent PCA (n?=?8), lymph node (n?=?166), bone (n?=?157) and other metastases (n?=?3) were 10.2, 5.9, 6.2, 7.4 and 3.8, respectively. The best cut-off values for differentiating non-pathological uptake in lymph nodes and bones from tumour uptake were found to be SUVmax of 3.2 and 1.9, respectively. Patients with PSA <2 had significantly lower SUVmax in bone metastases as compared to patients with PSA ≥2 (p?<?0.01).

Conclusions

This biodistribution study provided a broad range of uptake data of [⁶⁸Ga]PSMA-11 for normal organs/tissues, primary prostate tumours and metastatic lesions based on a large patient cohort. Both PT and small metastatic lesions were detectable due to their high tracer uptake. Four-times-higher median uptake in PT in comparison to normal prostate stroma resulted in a high diagnostic accuracy that could potentially be used for multimodal image-guided biopsy with dedicated reconstruction software.

     

Health-related outcomes of critically ill patients with and without sepsis

Purpose

To determine differences in health-related quality of life (HRQoL), survival and healthcare resource use of critically ill adults with and without sepsis.

Methods

We conducted a primary propensity score matched analysis of patients with and without sepsis enrolled in a large multicentre clinical trial. Outcomes included HRQoL at 6 months, survival to 2 years, length of ICU and hospital admission and cost of ICU and hospital treatment to 2 years.

Results

We obtained linked data for 3442 (97.3%) of 3537 eligible patients and matched 806/905 (89.0%) patients with sepsis with 806/2537 (31.7%) without. After matching, there were no significant differences in the proportion of survivors with and without sepsis reporting problems with mobility (37.8% vs. 38.7%, p?=?0.86), self-care (24.7% vs. 26.0%, p?=?0.44), usual activities (44.5% vs. 46.8%, p?=?0.28), pain/discomfort (42.4% vs. 41.6%, p?=?0.54) and anxiety/depression (36.9% vs. 37.7%, p?=?0.68). There was no significant difference in survival at 2 years: 482/792 (60.9%) vs. 485/799 (60.7%) (HR 1.01, 95% CI 0.86–1.18, p?=?0.94). The initial ICU and hospital admission were longer for patients with sepsis: 10.1?±?11.9 vs. 8.0?±?9.8 days (p?<?0.0001) and 22.8?±?21.2 vs. 19.1?±?19.0 days, (p?=?0.0003) respectively. The cost of ICU admissions was higher for patients with sepsis: A$43,345?±?46,263 (€35,109?±?35,043) versus 34,844?±?38,281 (€28,223?±?31,007), mean difference $8501 (€6885), 95% CI $4342–12,660 (€3517?±?10,254), p?<?0.001 as was the total cost of hospital treatment to 2 years: A$74,120?±?60,750 (€60,037?±?49,207) versus A$65,806?±?59,856 (€53,302?±?48,483), p?=?0.005.

Conclusions

Critically ill patients with sepsis have higher healthcare resource use and costs but similar survival and HRQoL compared to matched patients without sepsis.

     

Quantitative Analysis of [<Superscript>18</Superscript>F]FMISO PET for Tumor Hypoxia: Correlation of Modeling Results with Immunohistochemistry

Purpose

Quantitative evaluation of tumor hypoxia based on H-1-(3-[¹⁸F]fluoro-2-hydroxypropyl)-2-nitroimidazole ([¹⁸F]FMISO) positron emission tomography (PET) can deliver important information for treatment planning in radiotherapy. However, the merits and limitations of different analysis methods in revealing the underlying physiological feature are not clear. This study aimed to assess these quantitative analysis methods with the support of immunohistological data.

Procedures

Sixteen nude mice bearing xenografted human squamous cell carcinomas (FaDu or CAL-33) were scanned using 2-h dynamic [¹⁸F]FMISO PET. Tumors were resected and sliced, and the hypoxia marker pimonidazole was immunostained followed by H&E staining. The pimonidazole signal was segmented using a k-means clustering algorithm, and the hypoxic fraction (HF) was calculated as the hypoxic area/viable tumor-tissue-area ratio pooled over three tissue slices from the apical, center, and basal layers. PET images were analyzed using various methods including static analysis [standard uptake value (SUV), tumor-to-blood ratio (T/B), tumor-to-muscle ratio (T/M)] and kinetic modeling (Casciari αk _A , irreversible and reversible two-tissue compartment k ₃, Thorwarth w _A k ₃, Patlak K _i , Logan V _d , Cho K), and correlated with HF.

Results

No significant correlation was found for static analysis. A significant correlation between k ₃ of the irreversible two-tissue compartment model and HF was observed (r?=?0.61, p?=?0.01). The correlation between HF and αk _A of the Casciari model could be improved through reducing local minima by testing more sets of initial values (r?=?0.59, p?=?0.02) or by reducing the model complexity by fixing three parameters (r?=?0.63, p?=?0.0008).

Conclusions

With support of immunohistochemistry data, this study shows that various analysis methods for [¹⁸F]FMISO PET perform differently for assessment of tumor hypoxia. A better fitting quality does not necessarily mean a higher physiological correlation. Hypoxia PET analysis needs to consider both the mathematical stability and physiological fidelity. Based on the results of this study, preference should be given to the irreversible two-tissue compartment model as well as the Casciari model with reduced parameters.

     

Estimation of weight in adults from height: a novel option for a quick bedside technique

Purpose

In critical care situations, there are often neither the means nor the time to weigh each patient before administering strict weight-based drugs/procedures. A convenient, quick and accurate method is a priority in such circumstances for safety and effectiveness in emergent interventions as none exists in adults while those available are complex and yet to be validated. We aimed to study the correlation and accuracy of a quick bedside method of weight estimation in adults using height.

Method

The technique is estimated body weight—eBW(kg)?=?(N ??1)100, where ‘N’ is the measured height in metres.Adult undergraduates were enrolled 10/09/2015. Their heights and weights were measured while the formula was used to obtain the estimated weight. The SPSS version 21.0, Chicago, IL, USA was utilised for data analysis.

Results

We analysed 122 participants aged 21–38?years with height?=?1.55?m–1.95?m. The actual body weight range?=?48.0?kg–91.0 kg, mean?=?65.3?kg?±?9.7?kg and S.E.?=?2.0 while eBW?=?55 kg–95 kg, mean?=?69.1?kg?±?8.4?kg and S.E.?=?1.5. On BMI classes, a positive predictive value of 94.7% for the ‘normal’ category and 95.5% for ‘overweight’.Correlation coefficient at 99% confidence interval yielded (r)?=?+?1, (P?=?0.000) while the linear regression coefficient (r²)?=?+?1 at 95% confidence interval (P?=?0.000).The strength of agreement/precision was established by the Bland-Altman plot at 95%?±?2?s (P?=?0.000) and kappa statistic with value?=?0. 618.

Conclusion

This unprecedented statistical characterisation of the two weight estimate measures to have a good agreement scientifically proposes the utility of our method with the formula eBW(kg)?=?100(N?1) in critical care and ATLS protocol.

     

[<Superscript>18</Superscript>F]Fluorocholine Uptake of Parathyroid Adenoma Is Correlated with Parathyroid Hormone Level

Purpose

The aim of the study was to investigate the relationship between [¹⁸F]fluoromethyl-dimethyl-2-hydroxyethylammonium ([¹⁸F]FCh) positron emission tomography (PET) parameters, laboratory parameters, and postoperative histopathological results in patients with primary hyperparathyroidism (pHPT) due to parathyroid adenomas.

Procedures

This retrospective study was conducted in 52 patients with biochemically proven pHPT. [¹⁸F]FCh-PET parameters (maximum standardized uptake value: SUV_max) in early phase (after 2 min) and late phase (after 50 min), metabolic volume, and adenoma-to-background ratio (ABR), preoperative laboratory results (PTH and serum calcium concentration), and postoperative histopathology (location, size, volume, and weight of adenoma) were assessed. Relationship of PET parameters, laboratory parameters, and histopathological parameters was assessed using the Mann-Whitney U test and Spearman correlation coefficient. MRI characteristics of parathyroid adenomas were also analyzed.

Results

The majority of patients underwent a PET/MR scan, 42 patients (80.7 %); 10 patients (19.3 %) underwent PET/CT. We found a strong positive correlation between late-phase SUV_max and preoperative PTH level (r?=?0.768, p?<?0.001) and between late-phase ABR and preoperative PTH level (r?=?0.680, p?<?0.001). The surgical specimen volume was positively correlated with the PET/MR lesion volume (r?=?0.659, p?<?0.001). No significant association was observed between other [¹⁸F]FCh-PET parameters, laboratory parameters, and histopathological findings. Cystic adenomas were larger than non-cystic adenomas (p?=?0.048).

Conclusions

[¹⁸F]FCh uptake of parathyroid adenomas is strongly correlated with preoperative PTH serum concentration. Therefore, the preoperative PTH level might potentially be able to predict success of [¹⁸F]FCh-PET imaging in hyperparathyroidism, with higher lesion-to-background ratios being expected in patients with high PTH. PET/MR is accurate in estimating the volume of parathyroid adenomas.

     

Investigation of cis-4-[<Superscript>18</Superscript>F]Fluoro-D-Proline Uptake in Human Brain Tumors After Multimodal Treatment

Purpose

Cis-4-[¹⁸F]fluoro-D-proline (D-cis-[¹⁸F]FPro) has been shown to pass the intact blood-brain barrier and to accumulate in areas of secondary neurodegeneration and necrosis in the rat brain while uptake in experimental brain tumors is low. This pilot study explores the uptake behavior of D-cis-[¹⁸F]FPro in human brain tumors after multimodal treatment.

Procedures

In a prospective study, 27 patients with suspected recurrent brain tumor after treatment with surgery, radiotherapy, and/or chemotherapy (SRC) were investigated by dynamic positron emission tomography (PET) using D-cis-[¹⁸F]FPro (22 high-grade gliomas, one unspecified glioma, and 4 metastases). Furthermore, two patients with untreated lesions were included (one glioblastoma, one reactive astrogliosis). Data were compared with the results of PET using O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET) which detects viable tumor tissue. Tracer distribution, mean and maximum lesion-to-brain ratios (LBR_mean, LBR_max), and time-to-peak (TTP) of the time activity curve (TAC) of tracer uptake were evaluated. Final diagnosis was determined by histology (n?=?9), clinical follow-up (n?=?10), or by [¹⁸F]FET PET (n?=?10).

Results

D-cis-[¹⁸F]FPro showed high uptake in both recurrent brain tumors (n?=?11) and lesions classified as treatment-related changes (TRC) only (n?=?16) (LBR_mean 2.2?±?0.7 and 2.1?±?0.6, n.s.; LBR_max 3.4?±?1.2 and 3.2?±?1.3, n.s.). The untreated glioblastoma and the lesion showing reactive astrogliosis exhibited low D-cis-[¹⁸F]FPro uptake. Distribution of [¹⁸F]FET and D-cis-[¹⁸F]FPro uptake was discordant in 21/29 cases indicating that the uptake mechanisms are different.

Conclusion

The high accumulation of D-cis-[¹⁸F]FPro in pretreated brain tumors and TRC supports the hypothesis that tracer uptake is related to cell death. Further studies before and after therapy are needed to assess the potential of D-cis-[¹⁸F]FPro for treatment monitoring.

     

ACTH and cortisol responses to CRH in acute,subacute, and prolonged critical illness: a randomized,double-blind,placebo-controlled,crossover cohort study

Purpose

Low plasma ACTH in critically ill patients may be explained by shock/inflammation-induced hypothalamus-pituitary damage or by feedback inhibition exerted by elevated plasma free cortisol. One can expect augmented/prolonged ACTH-responses to CRH injection with hypothalamic damage, immediately suppressed responses with pituitary damage, and delayed decreased responses in prolonged critical illness with feedback inhibition.

Methods

This randomized, double-blind, placebo-controlled crossover cohort study, compared ACTH responses to 100 µg IV CRH and placebo in 3 cohorts of 40 matched patients in the acute (ICU-day 3–6), subacute (ICU-day 7–16) or prolonged phase (ICU-day 17–28) of critical illness, with 20 demographically matched healthy subjects. CRH or placebo was injected in random order on two consecutive days. Blood was sampled repeatedly over 135 min and AUC responses to placebo were subtracted from those to CRH.

Results

Patients had normal mean?±?SEM plasma ACTH concentrations (25.5?±?1.6 versus 24.8?±?3.6 pg/ml in healthy subjects, P?=?0.54) but elevated free cortisol concentrations (3.11?±?0.27 versus 0.58?±?0.05 µg/dl in healthy subjects, P?<?0.0001). The order of the CRH/placebo injections did not affect the ACTH responses, hence results were pooled. Patients in the acute phase of illness had normal mean?±?SEM ACTH responses (5149?±?848 pg/mL min versus 4120?±?688 pg/mL min in healthy subjects; P?=?0.77), whereas those in the subacute (2333?±?387 pg/mL min, P?=?0.01) and prolonged phases (2441?±?685 pg/mL min, P?=?0.001) were low, irrespective of sepsis/septic shock or risk of death.

Conclusions

Suppressed ACTH responses to CRH in the more prolonged phases, but not acute phase, of critical illness are compatible with feedback inhibition exerted by elevated free cortisol, rather than by cellular damage to hypothalamus and/or pituitary.

     

Quantitative inversion time prescription for myocardial late gadolinium enhancement using T1-mapping-based synthetic inversion recovery imaging: reducing subjectivity in the estimation of inversion time

To develop a quantitative T1-mapping-based synthetic inversion recovery (IR_synth) approach to calculate the optimal inversion time (TI₀) for late gadolinium enhancement (LGE) imaging. Prospectively enrolled patients (n?=?130, 58?±?16 years) underwent cardiac MRI on a 1.5T system including Look-Locker TI-scout (LL), modified LL IR (MOLLI)-based T1-mapping, and LGE acquisitions. Patients were randomized into two groups: LL group (TI-scout followed T1-mapping) or MOLLI group (T1-mapping followed TI-scout). In both groups, the second acquisition was used to determine the TI₀ for LGE. IR_synth images were generated from T1-maps between TI?=?200–400 ms in 5 ms increments. Image quality was rated on a 3-point scale and the remote/background signal intensity ratio (SIR) was calculated. In the LL group (n?=?53), the TI-scout-based TI₀ was significantly shorter compared to IR_synth [230 ms (219–242) vs. 280 ms (263–297), P?<?0.0001]. The TI₀ used for LGE was set 30–40 ms longer [261 ms (247–276), P?<?0.0001] than the TI-scout-based TI₀, resulting in a TI₀?~?20 ms shorter than what was obtained by IR_synth (P?=?0.0156). In the MOLLI group (n?=?63), IR_synth-based TI₀ was significantly longer than the TI-scout-based TI₀ [298 ms (262–334) vs. 242 ms (217–267), P?=?0.0313]. The quality of myocardial nulling was rated higher [2.4 (2.2–2.5) vs. 2.0 (1.8–2.1), P?=?0.0042] and the remote/background SIR was found to be more optimal (1.6 [1.1–2.1] vs. 2.6 [1.8–3.3], P?=?0.0256) in the MOLLI group. T1-based IR_synth selects TI₀ for LGE more accurately than conventional TI-scout imaging. IR_synth improves TI₀ selection by providing excellent visualization of the representative image contrast for LGE images, reducing operator dependence in LGE acquisition.     

Association of cardiovascular disease risk factors with left ventricular mass,biventricular function,and the presence of silent myocardial infarction on cardiac MRI in an asymptomatic population

The purposes of this study were to evaluate the relationship between risk factors for cardiovascular disease (CVD) and cardiac mass and function on cardiac magnetic resonance imaging (MRI), and to investigate possible risk factors for silent myocardial infarction (SMI) in an asymptomatic Asian population. We included 647 asymptomatic subjects (485 males, mean age 54.8?±?6.7 years; 162 females, mean age 55.2?±?7.6 years) who underwent 1.5-T cardiac MRI during a health checkup. The association between biventricular functional parameters as evaluated on MRI and CVD risk factors was examined using multivariable regression and analysis of variance. The left ventricular mass-to-volume ratios were positively related to body mass index (β?=?0.153, p?p?=?0.001) and diastolic (β?=?0.147, p?=?0.002) blood pressure, triglyceride levels (β?=?0.197, p?=?0.006), and C-reactive protein levels (β?=?0.130, p?p?=?0.025). No significant relationship was present between ventricular parameters and the presence of SMI after adjusting for confounders. The prevalence (6.9?%, 7/101) of SMI in diabetics was significantly greater than that in non-diabetics patients (0.9?%, 5/546; confidence interval 1.739–12.848; p?相似文献   

A mesenteric traction syndrome affects near-infrared spectroscopy evaluated cerebral oxygenation because skin blood flow increases

During abdominal surgery manipulation of internal organs may induce a “mesenteric traction syndrome” (MTS) including a triad of flushing, hypotension, and tachycardia that lasts for about 30 min. We evaluated whether MTS affects near-infrared spectroscopy (NIRS) assessed frontal lobe oxygenation (S_cO₂) by an increase in forehead skin blood flow (SkBF). The study intended to include 10 patients who developed MTS during pancreaticoduodenectomy and 22 patients were enrolled (age 61?±?8 years; mean?±?SD). NIRS determined ScO₂, laser Doppler flowmetry determined SkBF, cardiac output (CO) was evaluated by pulse-contour analysis (Modelflow), and transcranial Doppler assessed middle cerebral artery mean flow velocity (MCA V_mean). MTS was identified by flushing within 60 min after start of surgery. MTS developed 20 min (12–24; median with range) after the start of surgery and heart rate (78?±?16 vs. 68?±?17 bpm; P?=?0.0032), CO (6.2?±?1.4 vs. 5.3?±?1.1 L min^?1; P?=?0.0086), SkBF (98?±?35 vs. 80?±?23 PU; P?=?0.0271), and S_cO₂ (71?±?6 vs. 67?±?8%; P?<?0.0001), but not MCA V_mean (32?±?8 vs. 32?±?7; P?=?0.1881) were largest in the patients who developed MTS. In some patients undergoing abdominal surgery NIRS-determined S_cO₂ is at least temporarily affected by an increase in extra-cranial perfusion independent of cerebral blood flow as indicated by MCA V_mean. Thus, NIRS evaluation of S_cO₂ may overestimate cerebral oxygenation if patients flush during surgery.     

Simultaneous multi slice (SMS) balanced steady state free precession first-pass myocardial perfusion cardiovascular magnetic resonance with iterative reconstruction at 1.5 T

Background

Simultaneous-Multi-Slice (SMS) perfusion imaging has the potential to acquire multiple slices, increasing myocardial coverage without sacrificing in-plane spatial resolution. To maximise signal-to-noise ratio (SNR), SMS can be combined with a balanced steady state free precession (bSSFP) readout. Furthermore, application of gradient-controlled local Larmor adjustment (GC-LOLA) can ensure robustness against off-resonance artifacts and SNR loss can be mitigated by applying iterative reconstruction with spatial and temporal regularisation. The objective of this study was to compare cardiovascular magnetic resonance (CMR) myocardial perfusion imaging using SMS bSSFP imaging with GC-LOLA and iterative reconstruction to 3 slice bSSFP.

Methods

Two contrast-enhanced rest perfusion sequences were acquired in random order in 8 patients: 6-slice SMS bSSFP and 3 slice bSSFP. All images were reconstructed with TGRAPPA. SMS images were also reconstructed using a non-linear iterative reconstruction with L1 regularisation in wavelet space (SMS-iter) with 7 different combinations for spatial (λ_σ) and temporal (λ_τ) regularisation parameters. Qualitative ratings of overall image quality (0?=?poor image quality, 1?=?major artifact, 2?=?minor artifact, 3?=?excellent), perceived SNR (0?=?poor SNR, 1?=?major noise, 2?=?minor noise, 3?=?high SNR), frequency of sequence related artifacts and patient related artifacts were undertaken. Quantitative analysis of contrast ratio (CR) and percentage of dark rim artifact (DRA) was performed.

Results

Among all SMS-iter reconstructions, SMS-iter 6 (λ_σ 0.001 λ_τ 0.005) was identified as the optimal reconstruction with the highest overall image quality, least sequence related artifact and higher perceived SNR. SMS-iter 6 had superior overall image quality (2.50?±?0.53 vs 1.50?±?0.53, p?=?0.005) and perceived SNR (2.25?±?0.46 vs 0.75?±?0.46, p?=?0.010) compared to 3 slice bSSFP. There were no significant differences in sequence related artifact, CR (3.62?±?0.39 vs 3.66?±?0.65, p?=?0.88) or percentage of DRA (5.25?±?6.56 vs 4.25?±?4.30, p?=?0.64) with SMS-iter 6 compared to 3 slice bSSFP.

Conclusions

SMS bSSFP with GC-LOLA and iterative reconstruction improved image quality compared to a 3 slice bSSFP with doubled spatial coverage and preserved in-plane spatial resolution. Future evaluation in patients with coronary artery disease is warranted.

     

SPECT Imaging with <Superscript>99m</Superscript>Tc-Labeled EGFR-Specific Nanobody for <Emphasis Type="Italic">In Vivo</Emphasis> Monitoring of EGFR Expression

Purpose

Overexpression of the epidermal growth factor receptor (EGFR) occurs with high incidence in various carcinomas. The oncogenic expression of the receptor has been exploited for immunoglobulin-based diagnostics and therapeutics. We describe the use of a llama single-domain antibody fragment, termed Nanobody®, for the in vivo radioimmunodetection of EGFR overexpressing tumors using single photon emission computed tomography (SPECT) in mice.

Methods

Fluorescence-activated cell sorting (FACS) analysis was performed to evaluate the specificity and selectivity of 8B6 Nanobody to bind EGFR on EGFR overexpressing cells. The Nanobody was then labeled with ^99mTc via its C-terminal histidine tail. Uptake in normal organs and tissues was assessed by ex vivo analysis. In vivo tumor targeting of ^99mTc-8B6 Nanobody was evaluated via pinhole SPECT in mice bearing xenografts of tumor cells with either high (A431) or moderate (DU145) overexpression of EGFR.

Results

FACS analysis indicated that the 8B6 Nanobody only recognizes cells overexpressing EGFR. In vivo blood clearance of ^99mTc-8B6 Nanobody is relatively fast (half-life, 1.5 h) and mainly via the kidneys. At 3 h postinjection, total kidney accumulation is high (46.6?±?0.9%IA) compared to total liver uptake (18.9?±?0.6%IA). Pinhole SPECT imaging of mice bearing A431 xenografts showed higher average tumor uptake (5.2?±?0.5%IA/cm³) of ^99mTc-8B6 Nanobody compared to DU145 xenografts (1.8?±?0.3%IA/cm³, p?

Conclusion

The EGFR-binding Nanobody investigated in this study shows high specificity and selectivity towards EGFR overexpressing cells. Pinhole SPECT analysis with ^99mTc-8B6 Nanobody enabled in vivo discrimination between tumors with high and moderate EGFR overexpression. The favorable biodistribution further corroborates the suitability of Nanobodies for in vivo tumor imaging.