Role of [18F]FDG PET in prediction of KRAS and EGFR mutation status in patients with advanced non-small-cell lung cancer

Purpose

The tumour molecular profile predicts the activity of epidermal growth factor receptor (EGFR) inhibitors in non-small-cell lung cancer (NSCLC). However, tissue availability and tumour heterogeneity limit its assessment. We evaluated whether [¹⁸F]FDG PET might help predict KRAS and EFGR mutation status in NSCLC.

Methods

Between January 2005 and October 2011, 340 NSCLC patients were tested for KRAS and EGFR mutation status. We identified patients with stage III and IV disease who had undergone [¹⁸F]FDG PET/CT scanning for initial staging. SUVpeak, SUVmax and SUVmean of the single hottest tumour lesions were calculated, and their association with KRAS and EGFR mutation status was assessed. A receiver operator characteristic (ROC) curve analysis and a multivariate analysis (including SUVmean, gender, age and AJCC stage) were performed to identify the potential value of [¹⁸F]FDG PET/CT for predicting KRAS mutation.

Results

From 102 patients staged using [¹⁸F]FDG PET/CT, 28 (27 %) had KRAS mutation (KRAS+), 22 (22 %) had EGFR mutation (EGFR+) and 52 (51 %) had wild-type KRAS and EGFR profiles (WT). KRAS+ patients showed significantly higher [¹⁸F]FDG uptake than EGFR+ and WT patients (SUVmean 9.5, 5.7 and 6.6, respectively; p?18F]FDG uptake between EGFR+ patients and WT patients. ROC curve analysis for KRAS mutation status discrimination yielded an area under the curve of 0.740 for SUVmean (p?Conclusion NSCLC patients with tumours harbouring KRAS mutations showed significantly higher [¹⁸F]FDG uptake than WT patients, as assessed in terms of SUVpeak, SUVmax and SUVmean. A multivariate model based on age, gender, AJCC stage and SUVmean might be used as a predictive marker of KRAS mutation status in patients with stage III or IV NSCLC.     

Validation of a short-scan-time imaging protocol for thallium-201 myocardial SPECT with a multifocal collimator

Objective

IQ-SPECT (Siemens AG, Munich, Germany) is a highly sensitive single-photon-emission computed tomography (SPECT) myocardial perfusion imaging (MPI) system that uses a multifocal collimator. We searched for a suitable protocol for short-time imaging by IQ-SPECT in thallium-201 (Tl-201) MPI by evaluating phantom images and also by comparing human IQ-SPECT images with conventional SPECT images as reference standards.

Methods

We assessed the image quality using the normalized mean square error (NMSE) and drew up count profiles in Tl-201 SPECT images acquired with IQ-SPECT in a phantom study. We also performed Tl-201 stress myocardial SPECT/CT in 21 patients and compared delayed images acquired by using IQ-SPECT with 36 or 17 views per head with images obtained by using conventional SPECT.

Results

The NMSE of SPECT images from IQ-SPECT with 36 views was approximately one-fifth of that with 17 views. The myocardial count profile of images with 17 views was lower than those of images with 36 or 104 views in some regions. Defect scores were significantly lower, and image quality scores higher, in images from conventional SPECT than in those from IQ-SPECT with 17 views. Defect scores and image quality scores were equivalent in images from conventional SPECT and those from IQ-SPECT with 36 views. Agreement with the results of conventional SPECT in terms of coronary artery territory-based defect judgment was the best in IQ-SPECT with 36 views with computed tomography-derived attenuation correction (CTAC): the kappa values for IQ-SPECT with 36 views were 0.76 (without CTAC) and 0.83 (with CTAC), and those for IQ-SPECT with 17 views were 0.62 (without CTAC) and 0.59 (with CTAC). The difference in quantitative tracer uptake between conventional SPECT images and IQ-SPECT images was significantly greater for IQ-SPECT images with 17 views than for those with 36 views.

Conclusions

Scanning with 36 views per head with CTAC may be appropriate for Tl-201 MPI using IQ-SPECT, because it provides images equivalent to those using conventional SPECT.     

Impact of 18F-FDG PET/CT on the management of adrenocortical carcinoma: analysis of 106 patients

Purpose

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Limited data are available about on value of ¹⁸F-FDG PET/CT in ACC. We evaluated the impact of PET/CT on the management of ACC.

Methods

We performed a retrospective review in patients with ACC who had undergone PET/CT. The impact of PET/CT on the management plan was evaluated by comparing the findings on PET/CT to the findings on contrast-enhanced CT. The sensitivity, specificity, and accuracy of each form of imaging were calculated. The correlations between PET/CT parameters, including maximum standardized uptake value (SUV_max), total lesion glycolysis, and decline in SUV_max after chemotherapy, and clinical outcome were evaluated.

Results

Included in the analysis were 106 patients with 180 PET/CT scans. Of the 106 patients, 7 underwent PET/CT only for initial staging, 84 underwent PET/CT only for restaging, and 15 underwent PET/CT for both initial staging and restaging. PET/CT changed the management plan in 1 of 22 patients (5 %) at initial staging and 9 of 99 patients (9 %) at restaging. In 5 of the patients in whom PET/CT changed the management plan, PET/CT showed response to chemotherapy but contrast-enhanced CT showed stable disease. Sensitivity, specificity, and accuracy were 100 %, 100 %, and 100 % for PET/CT at initial staging; 92.6 %, 100 %, and 96.4 % for CT at initial staging; 98.4 %, 100 %, and 99.5 % for PET/CT at restaging; and 96.8 %, 98.6 %, and 98.0 % for CT at restaging, respectively. No PET/CT parameters were associated with survival at either initial diagnosis or recurrence.

Conclusion

PET/CT findings could substantially change the management plan in a small proportion of patients with ACC. Although lesion detection was similar between PET/CT and CT, PET/CT may be preferred for chemotherapeutic response assessment because it may predict response before anatomic changes are detected on CT.     

MR-sequences for prostate cancer diagnostics: validation based on the PI-RADS scoring system and targeted MR-guided in-bore biopsy

Purpose

This study evaluated the accuracy of MR sequences [T2-, diffusion-weighted, and dynamic contrast-enhanced (T2WI, DWI, and DCE) imaging] at 3T, based on the European Society of Urogenital Radiology (ESUR) scoring system [Prostate Imaging Reporting and Data System (PI-RADS)] using MR-guided in-bore prostate biopsies as reference standard.

Methods

In 235 consecutive patients [aged 65.7?±?7.9 years; median prostate-specific antigen (PSA) 8 ng/ml] with multiparametric prostate MRI (mp-MRI), 566 lesions were scored according to PI-RADS. Histology of all lesions was obtained by targeted MR-guided in-bore biopsy.

Results

In 200 lesions, biopsy revealed prostate cancer (PCa). The area under the curve (AUC) for cancer detection was 0.70 (T2WI), 0.80 (DWI), and 0.74 (DCE). A combination of T2WI + DWI, T2WI + DCE, and DWI + DCE achieved an AUC of 0.81, 0.78, and 0.79. A summed PI-RADS score of T2WI + DWI + DCE achieved an AUC of 0.81. For higher grade PCa (primary Gleason pattern?≥?4), the AUC was 0.85 for T2WI + DWI, 0.84 for T2WI + DCE, 0.86 for DWI + DCE, and 0.87 for T2WI + DWI + DCE. The AUC for T2WI + DWI + DCE for transitional-zone PCa was 0.73, and for the peripheral zone 0.88. Regarding higher-grade PCa, AUC for transitional-zone PCa was 0.88, and for peripheral zone 0.96.

Conclusion

The combination of T2WI + DWI + DCE achieved the highest test accuracy, especially in patients with higher-grade PCa. The use of ≤2 MR sequences led to lower AUC in higher-grade and peripheral-zone cancers.

Key Points

? T2WI + DWI + DCE achieved the highest accuracy in patients with higher grade PCa ? T2WI + DWI + DCE was more accurate for peripheral- than for transitional-zone PCa ? DCE increased PCa detection accuracy in the peripheral zone ? DWI was the leading sequence in the transitional zone     

Perfusion-metabolism coupling in recurrent gliomas: a prospective validation study with 13N-ammonia and 18F-fluorodeoxyglucose PET/CT

Introduction

We assessed the validity of “perfusion-metabolism coupling” hypothesis in recurrent glioma with ¹³N-ammonia (¹³N-NH₃) PET/CT and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT.

Methods

Fifty-six consecutive patients (age, 38.8?±?12.1 years; 62.5 % males) with histologically proven and previously treated glioma presenting with clinical suspicion of recurrence were prospectively enrolled and evaluated with ¹³N-NH₃ PET/CT and ¹⁸F-FDG PET/CT. PET/CT images were evaluated both qualitatively and semiquantitatively. Tumor to white matter uptake ratio (T/W) and tumor to gray matter uptake ratio (T/G) were calculated and analyzed for both the modalities. A combination of clinico-radiological follow-up, repeated imaging, and biopsy (when available) were considered as the reference standard.

Results

Based on the reference standard, 27/56 patients had recurrence. ¹³N-NH₃ PET/CT and ¹⁸F-FDG PET/CT were concordant in 55/56 patients. Overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ¹³N-NH₃PET/CT were 77.8, 86.2, 84.0, 80.7, and 82.1 %, respectively, and for ¹⁸F-FDG PET/CT were 77.8, 89.7, 87.5, 81.2, and 83.9 %, respectively. There was excellent agreement between results of ¹³N-NH₃ PET/CT and ¹⁸F-FDG PET/CT (??=?0.964; P?13N-NH₃ PET/CT and ¹⁸F-FDG PET/CT were not significantly different between high-grade and low-grade glioma (P?=?1.000). A strong positive correlation was noted between the uptake ratios derived on the two modalities (ρ?=?0.866, P?ρ?=?0.918, P?Conclusion A combination of ¹³N-NH₃ PET/CT and ¹⁸F-FDG PET/CT demonstrates that perfusion and metabolism are coupled in recurrent gliomas. These tracers target two different but interrelated aspects of the same pathologic process and can be used as surrogates for each other.     

Performance of FDG PET/CT at initial diagnosis in a rare lymphoma: nodular lymphocyte-predominant Hodgkin lymphoma

Purpose

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare Hodgkin lymphoma distinguished from classical Hodgkin lymphoma (cHL) by the nature of the neoplastic cells which express B-cell markers. We wanted to determine the diagnostic performance of FDG PET/CT in initial assessment and its therapeutic impact on staging.

Methods

We retrospectively studied a population of 35 patients with NLPHL (8 previously treated for NLHPL, 27 untreated). All patients underwent an initial staging by pretherapeutic FDG PET/CT. The impact on initial stage or relapse stage was assessed by an independent physician.

Results

In a per-patient analysis, the sensitivity of the pretherapeutic FDG PET/CT was 100 %. In a per-site analysis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of pretherapeutic FDG PET/CT were 100 %, 99 %, 97 %, 100 % and 99 %, respectively. Pretherapeutic FDG PET/CT led to a change in the initial stage/relapse stage in 12 of the 35 patients (34 %). In contrast to previous results established without FDG PET/CT, 20 % of patient had osteomedullary lesions.

Conclusion

Pretherapeutic FDG PET/CT has excellent performance for initial staging or relapse staging of NLPHL.     

Comparison of the prognostic values of 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT in patients with well-differentiated neuroendocrine tumor

Purpose

To determine the prognostic value of ⁶⁸Ga-DOTANOC PET/CT in patients with well-differentiated neuroendocrine tumor (NET), and to compare the prognostic value with that of ¹⁸F-FDG PET/CT and other conventional clinicopathological prognostic factors.

Methods

Data from 37 consecutive patients (age 46.6?±?13.5 years, 51 % men) with well-differentiated NET who underwent ⁶⁸Ga-DOTANOC PET/CT and ¹⁸F-FDG PET/CT were analyzed. All patients underwent a baseline visit with laboratory and radiological examinations. Clinical and imaging follow-up was performed in all patients. Progression-free survival (PFS) was measured from the date of the first PET/CT scan to the first documentation of progression of disease.

Results

⁶⁸Ga-DOTANOC PET/CT was positive in 37 of the 37 patients and ¹⁸F-FDG PET/CT was positive in 21. During follow-up 10 patients (27 %) showed progression of disease and 27 (73 %) showed no progression (24 stable disease, 3 partial response). The median follow-up was 25 months (range 2 – 52 months). Among the variables evaluated none was significantly different between the progressive disease and nonprogressive disease groups, with only SUVmax on ⁶⁸Ga-DOTANOC PET/CT being borderline significant (P?=?0.073). In the univariate analysis for PFS outcome, SUVmax on ⁶⁸Ga-DOTANOC PET/CT (HR 0.122, 95 % CI 0.019 – 0.779; P?=?0.026) and histopathological tumor grade (HR 4.238, 95 % CI 1.058 – 16.976; P?=?0.041) were found to be associated with PFS. Other factors including age, sex, primary site, Ki-67 index, TNM stage, ¹⁸F-FDG PET/CT status (positive/negative), SUVmax on ¹⁸F-FDG PET/CT and type of treatment were not significant. In multivariable analysis, only SUVmax on ⁶⁸Ga-DOTANOC PET/CT was found to be an independent positive predictor of PFS (HR 0.122, 95 % CI 0.019 – 0.779; P?=?0.026).

Conclusion

SUVmax measured on ⁶⁸Ga-DOTANOC PET/CT is an independent, positive prognostic factor in patients with well-differentiated NET and is superior to SUVmax on ¹⁸F-FDG PET/CT and conventional clinicopathological factors for predicting PFS.     

18F-fluorodeoxyglucose positron emission tomography combined with whole-body computed tomographic angiography in critically ill patients with suspected severe sepsis with no definite diagnosis

Purpose

Timely identification of septic foci is critical in patients with severe sepsis or septic shock of unknown origin. This prospective pilot study aimed to assess ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET), combined with whole-body computed tomographic angiography (CTA), in patients with suspected severe sepsis and for whom the prior diagnostic workup had been inconclusive.

Methods

Patients hospitalized in an intensive care unit with a suspected severe sepsis but no definite diagnosis after 48 h of extensive investigations were prospectively included and referred for a whole body FDG-PET/CTA. Results from FDG-PET/CTA were assessed according to the final diagnosis obtained after follow-up and additional diagnostic workup.

Results

Seventeen patients were prospectively included, all on mechanical ventilation and 14 under vasopressor drugs. The FDG-PET/CTA exam 1) was responsible for only one desaturation and one hypotension, both quickly reversible under treatment; 2) led to suspect 16 infectious sites among which 13 (81 %) could be confirmed by further diagnostic procedures; and 3) triggered beneficial changes in the medical management of 12 of the 17 study patients (71 %). The FDG-PET/CTA images showed a single or predominant infectious focus in two cases where CTA was negative and in three cases where CTA exhibited multiple possible foci.

Conclusion

Whole-body FDG-PET/CTA appears to be feasible, relatively safe, and provides reliable and useful information, when prospectively planned in patients with suspected severe sepsis and for whom prior diagnostic workup had been inconclusive. The FDG-PET images are particularly helpful when CTA exhibits no or multiple possible sites.     

Efficacy of preoperative transcatheter arterial chemoembolization combined with systemic chemotherapy for treatment of unresectable hepatoblastoma in children

Purpose

The purpose of this study was to evaluate, retrospectively, the clinical efficacy of preoperative transcatheter arterial chemoembolization (TACE) combined with systemic chemotherapy for unresectable hepatoblastoma.

Materials and methods

Five boys and three girls (mean age 15.2 months) were treated with preoperative TACE combined with systemic chemotherapy for unresectable hepatoblastomas. Mean tumor diameter and mean alfa-fetoprotein (AFP) level were 11.8 cm and 549,386 ng/mL, respectively. Pretreatment, the extent of disease (PRETEXT) was: II, 1; III, 6; IV, 1. For all patients, preoperative systemic chemotherapy was administered before TACE. At each TACE, carboplatin and adriamycin mixed with iodized oil were infused into the feeding arteries. Tumor response and prognosis after treatment were evaluated.

Results

TACE resulted in few Grade 1 adverse effects (AEs), without G3 or more AEs, according to CTACAE 3.0. Mean tumor shrinkage was 60.9 %, and the mean AFP decrease from initial levels was 94.8 %. In all cases TACE combined with systemic chemotherapy enabled subsequent safe and complete surgical resection. After a mean follow-up of 59 months, tumor-free survival was 75 %.

Conclusion

Preoperative TACE combined with systemic chemotherapy was effective in inducing surgical resectability of unresectable hepatoblastoma.     

Brain perfusion with intracarotid injection of99mTc-HM-PAO in partial epilepsy during amobarbital testing

Technetium (^99mTc) hexamethyl propylene amine oxime (HM-PAO) was injected into the internal carotid artery in ten epileptic patients after the end of amobarbital speech-memory tests. The cerebral perfusion as visualized from SPET was compared to cerebral angiographies, which showed unilateral filling of intracranial vessels in seven patients. SPET revealed cross-flow between the hemispheres in four of these seven patients. In three patients in whom the angiograms had shown bilateral contrast filling, SPET showed cross-flow in only two. It is concluded that^99mTc-HM-PAO SPET examinations provide valuable information for correct interpretation of amobarbital tests on cognitive hemisphere functions. The SPET technique may help to explain atypical speech and memory responses caused by unusual intracranial vascularization.     

Comparison of choline-PET/CT,MRI, SPECT,and bone scintigraphy in the diagnosis of bone metastases in patients with prostate cancer: a meta-analysis

Published data on the diagnosis of bone metastases of prostate cancer are conflicting and heterogeneous. We performed a comprehensive meta-analysis to compare the diagnostic performance of choline-PET/CT, MRI, bone SPECT, and bone scintigraphy (BS) in detecting bone metastases in parents with prostate cancer. Pooled sensitivity, specificity, and diagnostic odds ratios (DOR) were calculated both on a per-patient basis and on a per-lesion basis. Summary receiver operating characteristic (SROC) curves were also drawn to obtain the area under curve (AUC) and Q* value. Sixteen articles consisting of 27 studies were included in the analysis. On a per-patient basis, the pooled sensitivities by using choline PET/CT, MRI, and BS were 0.91 [95 % confidence interval (CI): 0.83–0.96], 0.97 (95 % CI: 0.91–0.99), 0.79 (95 % CI: 0.73–0.83), respectively. The pooled specificities for detection of bone metastases using choline PET/CT, MRI, and BS, were 0.99 (95 % CI: 0.93–1.00), 0.95 (95 % CI: 0.90–0.97), and 0.82 (95 % CI: 0.78–0.85), respectively. On a per-lesion basis, the pooled sensitivities of choline PET/CT, bone SPECT, and BS were 0.84 (95 % CI: 0.81–0.87), 0.90 (95 % CI: 0.86–0.93), 0.59 (95 % CI: 0.55–0.63), respectively. The pooled specificities were 0.93 (95 % CI: 0.89–0.96) for choline PET/CT, 0.85 (95 % CI: 0.80–0.90) for bone SPECT, and 0.75 (95 % CI: 0.71–0.79) for BS. This meta-analysis indicated that MRI was better than choline PET/CT and BS on a per-patient basis. On a per-lesion analysis, choline PET/CT with the highest DOR and Q* was better than bone SPECT and BS for detecting bone metastases from prostate cancer.     

Physiologic characterization of inflammatory arthritis in a rabbit model with BOLD and DCE MRI at 1.5 Tesla

Objective

Our aim was to test the feasibility of blood oxygen level dependent magnetic resonance imaging (BOLD MRI) and dynamic contrast-enhanced (DCE) MRI to monitor periarticular hypoxic/inflammatory changes over time in a juvenile rabbit model of arthritis.

Methods

We examined arthritic and contralateral nonarthritic knees of 21 juvenile rabbits at baseline and days 1,14, and 28 after induction of arthritis by unilateral intra-articular injection of carrageenin with BOLD and DCE MRI at 1.5 Tesla (T). Nine noninjected rabbits served as controls. Associations between BOLD and DCE-MRI and corresponding intra-articular oxygen pressure (PO₂) and blood flow [blood perfusion units (BPU)] (polarographic probes, reference standards) or clinical–histological data were measured by correlation coefficients.

Results

Percentage BOLD MRI change obtained in contralateral knees correlated moderately with BPU on day 0 (r?=??0.51, p?=?0.02) and excellently on day 28 (r?=??0.84, p?=?0.03). A moderate correlation was observed between peak enhancement DCE MRI (day 1) and BPU measurements in arthritic knees (r?=?0.49, p?=?0.04). In acute arthritis, BOLD and DCE MRI highly correlated (r?=?0.89, p?=?0.04; r?=?1.0, p?Conclusion The proposed techniques are feasible to perform at 1.5 T, and they hold potential as surrogate measures to monitor hypoxic and inflammatory changes over time in arthritis at higher-strength MRI fields.

Key points

? BOLD and DCE MRI detect interval perisynovial changes in a rabbit knee ? BOLD and DCE MRI act as surrogate markers of physiologic changes in arthritis ? BOLD MRI signal represents oxygen extraction compared with intra-articular PO ₂ ? DCE MRI measurements estimate physiologic periarticular vascular properties ? In rabbit knees with acute arthritis, BOLD/DCE MRI highly correlated with histological scores     

Prognostic Value of Metabolic Tumor Volume Estimated by 18 F-FDG Positron Emission Tomography/Computed Tomography in Patients with Diffuse Large B-Cell Lymphoma of Stage II or III Disease

Purpose

The purpose of this study was to evaluate the prognostic value of metabolic tumor volume (MTV) measured by ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-containing immunochemotherapy.

Methods

Patients with newly diagnosed DLBCL who underwent pre-treatment torso FDG-PET/CT scan taken within 10 days before treatment were included. MTV was defined as the volume of hypermetabolic tissue with a standardized uptake value (SUV) greater than a threshold value of 2.5 and calculated using volume viewer software. Association of MTV with patient characteristics and survival were compared.

Results

A total of 96 patients were evaluated. During a median follow-up period of 27.8 months, 3-year event-free survival (EFS) and overall survival was 69.5 % and 72.9 %, respectively. The Ann Arbor staging showed a limitation of prognosis because there was no difference of EFS between patients with Ann Arbor stage II and those with stage III. On the contrary, among patients with Ann Arbor stage II or III disease (n?=?53), the higher MTV group showed significantly inferior EFS compared with the lower MTV group.

Conclusions

In the current study, we identified the pre-treatment MTV measured by FDG-PET/CT as a potential predictor of survival in patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), at least in Ann Arbor stage II and III disease.     

Ultrafast cone-beam computed tomography imaging and postprocessing data during image-guided therapeutic practice

Objective

Our objective was to evaluate ultrafast cone-beam computed tomography (u-CBCT) image data using cross-sectional images, perfusion blood volume (PBV), and image fusion during tumour detection at the course of transarterial chemoembolization.

Methods

One hundred and fifty patients (63?±?20 years; 33–82) were examined from February to October 2013 with u-CBCT. Tumour delineation and conspicuity were determined using u-CBCT cross-sectional PBV and u-CBCT-magnetic resonance imaging (MRI) fused data sets for hyperenhanced (HYET), heterogeneously enhanced (HEET), and unenhanced (UET) tumour categories. Catheter localisation and tumour feeding vessels were assessed using all data sets. Quantitative and qualitative analyses were performed using appropriate statistical tests.

Result

Qualitative and quantitative tumour delineation showed significant difference (all P?P?P?Conclusion Tumour delineation was clearly possible using u-CBCT cross sections with contrast material. PBV uses color-coded images to increase detection and produces good tumour differentiation. Image fusion helps accurately identify tumour and feeding vessels and locate contrast material injection sites and catheter tips without additional data acquisition.

Key points

? Ultrafast CBCT cross-sectional data provide good tumour delineation with contrast material ? Postprocessed PBV using u-CBCT increased detectability and tumour differentiation ? u-CBCT cross-sectional PBV and u-CBCT-MRI data helps image guidance during chemoembolization ? u-CBCT-MRI can identify tumours and feeding vessels and locate catheter tip accurately     

Diagnostic value of FDG-PET/(CT) in children with fever of unknown origin and unexplained fever during immune suppression

Purpose

Fever of unknown origin (FUO) and unexplained fever during immune suppression in children are challenging medical problems. The aim of this study is to investigate the diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and FDG-PET combined with computed tomography (FDG-PET/CT) in children with FUO and in children with unexplained fever during immune suppression.

Methods

All FDG-PET/(CT) scans performed in the Radboud university medical center for the evaluation of FUO or unexplained fever during immune suppression in the last 10 years were reviewed. Results were compared with the final clinical diagnosis.

Results

FDG-PET/(CT) scans were performed in 31 children with FUO. A final diagnosis was established in 16 cases (52 %). Of the total number of scans, 32 % were clinically helpful. The sensitivity and specificity of FDG-PET/CT in these patients was 80 % and 78 %, respectively. FDG-PET/(CT) scans were performed in 12 children with unexplained fever during immune suppression. A final diagnosis was established in nine patients (75 %). Of the total number of these scans, 58 % were clinically helpful. The sensitivity and specificity of FDG-PET/CT in children with unexplained fever during immune suppression was 78 % and 67 %, respectively.

Conclusions

FDG-PET/CT appears a valuable imaging technique in the evaluation of children with FUO and in the diagnostic process of children with unexplained fever during immune suppression. Prospective studies of FDG-PET/CT as part of a structured diagnostic protocol are warranted to assess the additional diagnostic value.     

Assessment of an intermediate reprojection technique transitioning from planar to SPECT radionuclide ventriculography

Background

The technique of SPECT-RNV (radionuclide ventriculography) offers a greater amount of clinically usable data than its planar counterpart (P-RNV). In transitioning from planar to SPECT-only acquisition methodologies, reprojection of the SPECT data can provide a planar dataset which can be used as an interim technique. The aim of this study was to test if reprojected planar images could be used as a surrogate for true planar images in SPECT-only setting.

Methods

We performed SPECT-RNV and P-RNV on 47 patients on traditional sodium iodide (NaI) cameras, determining left ventricular ejection fractions (LVEF) for planar (EF_P) and SPECT (EF_S) techniques. We reprojected the SPECT-RNV data along the best septal separation angle determined from planar scanning. This creates a further planar dataset denoted ‘reprojected P-RNV’ (rP-RNV) giving a reprojected ejection fraction (EF_R) which can be used as a validation variable in transitioning to SPECT-only acquisition.

Results

Performing t tests showed no statistical difference between EF_P and EF_R (P > .017) but bias was observed in EF_S results compared to EF_P and EF_S compared to EF_R results. An unblinded, comparison of parametric data between the three datasets for a subset of ten patients showed good clinical concordance. False negative and false positive rates were low for rP-RNV compared to P-RNV.

Conclusions

The reprojected planar LVEF correlates well to P-RNV EF values. The rP-RNV dataset can aid clinicians in transitioning from planar RNV to SPECT-only acquisition.     

Effectiveness of contrast-enhanced ultrasound in the classification and emergency management of abdominal trauma

Objective

To analyse the correlation between contrast-enhanced ultrasound (CEUS)-based classification of the severity of abdominal parenchymal organ trauma and clinical outcomes, and to explore CEUS in classifying patients with such trauma, expecting that the use of CEUS will potentially enhance the quality and speed of the emergency management of abdominal trauma.

Methods

Three hundred six consecutive patients with blunt abdominal parenchymal organ trauma who received CEUS examination were retrospectively analysed. Two CEUS radiologists (identified as Reader A and Reader B in this study) who were not involved in the CEUS examinations of the patients were then asked to classify the patients independently according to their CEUS results. The classification results were later compared with patients’ clinical outcomes using Spearman’s rank correlation.

Results

The final clinical outcomes showed that 25.5 % (78/306) of patients received conservative treatment, 52.0 % (159/306) received minimally invasive treatment, and 22.5 % (69/306) received surgery. Spearman's rank correlation coefficients between the CEUS-based classification and clinical outcome were 0.952 from Reader A and 0.960 from Reader B.

Conclusions

CEUS can play an important role in the emergency management of abdominal trauma through the classification of patients for different treatment methods.

Key points

? The severity of abdominal trauma was classified by contrast-enhanced ultrasound (CEUS) ? There was a high correlation between CEUS-based classification and clinical outcomes ? CEUS-based classification is helpful for surgeons in the emergency management of abdominal trauma     

Does secretin stimulation add to magnetic resonance cholangiopancreatography in characterising pancreatic cystic lesions as side-branch intraductal papillary mucinous neoplasm?

Objectives

To assess the value of secretin during magnetic resonance cholangiopancreatography (MRCP) in demonstrating communication between cystic lesions and the pancreatic duct to help determine the diagnosis of side-branch intraductal papillary mucinous neoplasm (SB-IPMN).

Methods

This is an IRB-approved, HIPAA-compliant retrospective study of 29 SB-IPMN patients and 13 non-IPMN subjects (control) who underwent secretin-enhanced MRCP (s-MRCP). Two readers blinded to the final diagnosis reviewed three randomised image sets: (1) pre-secretin HASTE, (2) dynamic s-MRCP and (3) post-secretin HASTE. Logistic regression, generalised linear models and ROC analyses were used to compare pre- and post-secretin results.

Results

There was no significant difference in median scores for the pre-secretin [reader 1: 1; reader 2: 2 (range -2 to 2)] and post-secretin HASTE [reader 1: 1; reader 2: 1 (range -2 to 2)] in the SB-IPMN group (P?=?0.14), while the scores were lower for s-MRCP [reader 1: 0.5 (range -2 to 2); reader 2: 0 (range -1 to 2); P?=?0.016]. There was no significant difference in mean maximum diameter of SB-IPMN on pre- and post-secretin HASTE, and s-MRCP (P?>?0.05).

Conclusion

Secretin stimulation did not add to MRCP in characterising pancreatic cystic lesions as SB-IPMN.

Key Points

? Magnetic resonance cholangiopancreatography (MRCP) is used to evaluate pancreatic cystic lesions. ? Intraductal papillary mucinous neoplasm (IPMN) is a type of pancreatic cystic neoplasm. ? Secretin administration does not facilitate the diagnosis of IPMN on MRCP.     

New possibilities for volumetric-modulated arc therapy using the AgilityTM 160-leaf multileaf collimator

Purpose

This study compares the quality of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans optimized for an Elekta Agility^TM (Elekta, Stockholm, Sweden) multileaf collimator (MLC; leaf width 5 mm) and an Elekta MLCi2 (leaf width 10 mm) for complex target volumes (anal, AC; head and neck, H&N and prostate cancer, PC).

Patients and methods

For plan comparisons, 15 patients who had been treated with IMRT or VMAT using the MLCi2 were selected. For each patient, a retrospective treatment plan using the MLCi2 for the technique not applied was created, as were treatment plans for both techniques using the Agility^TM MLC. Dose–volume histograms (DHVs) for planning target volumes (PTVs) and organs at risk (OARs) were compared. Further parameters relating to dose conformity, dose homogeneity and mean dose (D_mean) to the PTV, compliance with the intended OAR dose criteria and overall dose to normal tissue were analyzed. Verification measurements were performed and optimization and treatment times were compared.

Results

Compared to the MLCi2 plans, the Agility^TM IMRT and VMAT plans show better or equivalent results in terms of PTV dose conformity and homogeneity. Compliance with the intended OAR dose criteria does not differ according to technique or MLC type. Slight differences are shown for dose distributions in OARs and normal tissue. Verification measurements show that all plans fulfill the acceptance criteria of a minimum of 95 % matched dose points for the 3 %/3 mm γ criterion. Optimization times for the VMAT plans increase compared to the IMRT plans, whereas treatment times decrease.

Conclusion

With the MLCi2, treatment of complex target volumes with VMAT was only possible with compromises in terms of target coverage. Using the Agility^TM MLC, even complex target volumes can be treated with VMAT without compromising target coverage or resulting in higher exposure of OARs or normal tissue.     

Influence of TNF-α and biomechanical stress on matrix metalloproteinases and lysyl oxidases expressions in human knee synovial fibroblasts

Purpose

It was reported that not only ACL but also the synovium may be the major regulator of matrix metalloproteinases (MMPs) in synovial fluids after ACL injury. In order to further confirm whether synovium is capable of regulating the microenvironment in the process of ACL injury, the complicated microenvironment of joint cavity after ACL injury was mimicked and the combined effects of mechanical injury and inflammatory factor [tumour necrosis factor-α (TNF-α)] on expressions of lysyl oxidases (LOXs) and MMPs in synovial fibroblasts derived from normal human synovium were studied.

Methods

Human normal knee joint synovial fibroblasts were stimulated for 1–6 h with mechanical stretch and inflammatory factor (TNF-α). Total RNA was harvested, reverse transcribed and assessed by real-time polymerase chain reaction for the expression of LOXs and MMP-1, 2, 3 messenger RNAs. MMP-2 activity was assayed from the collected culture media samples using zymography.

Results

Compared to control group, our results showed that 6 % physiological stretch increased MMP-2 and LOXs (except LOXL-3), decreased MMP-1 and MMP-3; injurious stretch (12 %) decreased LOXs (except LOXL-2)and increased MMP-1, 2 and 3; the combination of injurious stretch and TNF-α decreased LOXs and increased MMP-1, 2 and 3 in synovial fibroblasts in a synergistical manner.

Conclusion

This study demonstrated that combination of mechanical injury and inflammatory factors up-regulated the expressions of MMPs and down-regulated the expressions of LOXs in synovial fibroblasts, eventually alter the balance of tissue healing. Thus, synovium may be involved in regulating the microenvironment of joint cavity. Based on the mechanism, early interventions to inhibit the production of MMPs or promote the production of LOXs in the synovial fibroblasts should be performed to facilitate the healing of tissue.