How to Provide Gadolinium-Free PET/MR Cancer Staging of Children and Young Adults in Less than 1 h: the Stanford Approach

Purpose

To provide clinically useful gadolinium-free whole-body cancer staging of children and young adults with integrated positron emission tomography/magnetic resonance (PET/MR) imaging in less than 1 h.

Procedures

In this prospective clinical trial, 20 children and young adults (11–30 years old, 6 male, 14 female) with solid tumors underwent 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) PET/MR on a 3T PET/MR scanner after intravenous injection of ferumoxytol (5 mg Fe/kg) and [¹⁸F]FDG (2–3 MBq/kg). Time needed for patient preparation, PET/MR image acquisition, and data processing was compared before (n = 5) and after (n = 15) time-saving interventions, using a Wilcoxon test. The ferumoxytol-enhanced PET/MR images were compared with clinical standard staging tests regarding radiation exposure and tumor staging results, using Fisher’s exact tests.

Results

Tailored workflows significantly reduced scan times from 36 to 24 min for head to mid thigh scans (p < 0.001). These streamlined PET/MR scans were obtained with significantly reduced radiation exposure (mean 3.4 mSv) compared to PET/CT with diagnostic CT (mean 13.1 mSv; p = 0.003). Using the iron supplement ferumoxytol “off label” as an MR contrast agent avoided gadolinium chelate administration. The ferumoxytol-enhanced PET/MR scans provided equal or superior tumor staging results compared to clinical standard tests in 17 out of 20 patients. Compared to PET/CT, PET/MR had comparable detection rates for pulmonary nodules with diameters of equal or greater than 5 mm (94 vs. 100 %), yet detected significantly fewer nodules with diameters of less than 5 mm (20 vs 100 %) (p = 0.03). [¹⁸F]FDG-avid nodules were detected with slightly higher sensitivity on the PET of the PET/MR compared to the PET of the PET/CT (59 vs 49 %).

Conclusion

Our streamlined ferumoxytol-enhanced PET/MR protocol provided cancer staging of children and young adults in less than 1 h with equivalent or superior clinical information compared to clinical standard staging tests. The detection of small pulmonary nodules with PET/MR needs to be improved.

     

Evaluation of [<Superscript>18</Superscript>F]CP18 as a Substrate-Based Apoptosis Imaging Agent for the Assessment of Early Treatment Response in Oncology

Purpose

The substrate-based positron emission tomography (PET) tracer [¹⁸F]CP18 is capable of detecting the activity of caspase-3/7, two key executioner proteases in the apoptosis pathway, through selective cleavage of the ligand by the activated proteases and subsequent accumulation in apoptotic cells. Using an in vitro and in vivo model of colorectal cancer (CRC), we investigated whether [¹⁸F]CP18 tracer accumulation provides a measure for apoptosis and reliably reflects early treatment response to chemotherapeutics.

Procedures

[¹⁸F]CP18 cell uptake was assessed in treated Colo205 cells (saline, 5-fluorouracil (5-FU), irinotecan or their combination) and correlated with caspase-3/7 activity. [¹⁸F]CP18 imaging was performed in Colo205 xenografts, starting with a baseline μPET/micro X-ray computed tomography (?μCT) scan, followed by a 3-day treatment with saline (n = 5), 5-FU (low sensitivity, n = 4), irinotecan (high sensitivity, n = 5), or a combination of both (n = 7). The study was concluded with a second [¹⁸F]CP18 scan, 24 h after final treatment administration, followed by tumor removal for gamma counting (%ID/g) and for cleaved caspase-3 immunohistochemistry (apoptotic index/necrosis). Tumors were delineated on μCT images and, using the obtained volumes of interest, average percentage injected dose per cubic centimeter (%ID/cm³) was calculated from every μPET image.

Results

In vitro, [¹⁸F]CP18 cell uptake was positively correlated with caspase-3/7 activity (r = 0.59, p = 0.003). A drug-dependent increase in [¹⁸F]CP18 tumor uptake compared to baseline was observed in animals treated with 5-FU (+14 ± 25 %), irinotecan (+56 ± 54 %), and their combination (+158 ± 69 %, p = 0.002). %ID/cm³ showed a positive relationship with both %ID/g (r = 0.83, p < 0.0001) and the apoptotic index (r = 0.60, p = 0.004), but not with tumor necrosis (r = 0.22, p = 0.36).

Conclusion

Both our in vitro and in vivo findings have shown the ability of [¹⁸F]CP18-PET to visualize therapy-induced cancer cell apoptosis and possibly serve as a biomarker for early therapy response.

     

MR-imaging features of hepatocellular carcinoma capsule appearance in cirrhotic liver: comparison of gadoxetic acid and gadobenate dimeglumine

Purpose

The purpose of the study is to compare the MR-imaging features of hepatocellular carcinoma (HCC) capsule appearance on gadoxetic acid and gadobenate dimeglumine-enhanced MR imaging, using imaging-based presumptive diagnosis of HCC as the reference standard.

Methods

Gadoxetic acid and gadobenate dimeglumine-enhanced MR imaging of 51 patients with 71 HCCs were retrospectively reviewed. Three readers graded in consensus, using a five-point scale, the presence (score 4–5) of capsule appearance on images obtained during T1-weighted GRE portal venous phase (PVP), 3-min phase, and hepatobiliary phase (HBP). The Fisher's exact test and the t student unpaired test were performed.

Results

A hyperintense capsule appearance was present either on PVP or 3-min phase in 11/46 and in 24/25 HCCs imaged with gadoxetic acid and gadobenate dimeglumine-enhanced MR imaging, respectively (24% vs. 96% p < 0.001). A hypointense capsule appearance was present on HBP in 8/46 and 0/22 HCCs evaluated with gadoxetic acid and gadobenate dimeglumine-enhanced MR imaging, respectively (17% vs. 0% p = 0.046). A capsule appearance was detected either on PVP, 3-min phase, or HBP in 17/46 (37%) HCCs after gadoxetic acid injection and in 24/25 (96%) HCCs after gadobenate dimeglumine injection (p < 0.001).

Conclusions

A capsule appearance was more frequently seen on gadobenate dimeglumine-enhanced MR imaging when compared to gadoxetic acid-enhanced MR imaging.

     

On the use of approximate entropy and sample entropy with centre of pressure time-series

Background

Approximate entropy (ApEn) and sample entropy (SampEn) have been previously used to quantify the regularity in centre of pressure (COP) time-series in different experimental groups and/or conditions. ApEn and SampEn are very sensitive to their input parameters: m (subseries length), r (tolerance) and N (data length). Yet, the effects of changing those parameters have been scarcely investigated in the analysis of COP time-series. This study aimed to investigate the effects of changing parameters m, r and N on ApEn and SampEn values in COP time-series, as well as the ability of these entropy measures to discriminate between groups.

Methods

A public dataset of COP time-series was used. ApEn and SampEn were calculated for m?=?{2, 3, 4, 5}, r?=?{0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5} and N?=?{600, 1200} (30 and 60?s, respectively). Subjects were stratified in young adults (age?<?60, n?=?85), and older adults (age?≥?60) with (n?=?18) and without (n?=?56) falls in the last year. The effects of changing parameters m, r and N on ApEn and SampEn were investigated with a three-way ANOVA. The ability of ApEn and SampEn to discriminate between groups was investigated with a mixed ANOVA (within-subject factors: m, r and N; between-subject factor: group). Specific combinations of m, r and N producing significant differences between groups were identified using the Tukey’s honest significant difference procedure.

Results

A significant three-way interaction between m, r and N confirmed the sensitivity of ApEn and SampEn to the input parameters. SampEn showed a higher consistency and ability to discriminate between groups than ApEn. Significant differences between groups were mostly observed in longer (N?=?1200) COP time-series in the anterior-posterior direction. Those differences were observed for specific combinations of m and r, highlighting the importance of an adequate selection of input parameters.

Conclusions

Future studies should favour SampEn over ApEn and longer time-series (≥ 60?s) over shorter ones (e.g. 30?s). The use of parameter combinations such as SampEn (m?=?{4, 5}, r?=?{0.25, 0.3, 0.35}) is recommended.

     

Characterization of Magneto-Endosymbionts as MRI Cell Labeling and Tracking Agents

Purpose

Magneto-endosymbionts (MEs) show promise as living magnetic resonance imaging (MRI) contrast agents for in vivo cell tracking. Here we characterize the biomedical imaging properties of ME contrast agents, in vitro and in vivo.

Procedures

By adapting and engineering magnetotactic bacteria to the intracellular niche, we are creating magneto-endosymbionts (MEs) that offer advantages relative to passive iron-based contrast agents (superparamagnetic iron oxides, SPIOs) for cell tracking. This work presents a biomedical imaging characterization of MEs including: MRI transverse relaxivity (r ₂) for MEs and ME-labeled cells (compared to a commercially available iron oxide nanoparticle); microscopic validation of labeling efficiency and subcellular locations; and in vivo imaging of a MDA-MB-231BR (231BR) human breast cancer cells in a mouse brain.

Results

At 7T, r ₂ relaxivity of bare MEs was higher (250 s^?1 mM^?1) than that of conventional SPIO (178 s^?1 mM^?1). Optimized in vitro loading of MEs into 231BR cells yielded 1–4 pg iron/cell (compared to 5–10 pg iron/cell for conventional SPIO). r ₂ relaxivity dropped by a factor of ~3 upon loading into cells, and was on the same order of magnitude for ME-loaded cells compared to SPIO-loaded cells. In vivo, ME-labeled cells exhibited strong MR contrast, allowing as few as 100 cells to be detected in mice using an optimized 3D SPGR gradient-echo sequence.

Conclusions

Our results demonstrate the potential of magneto-endosymbionts as living MR contrast agents. They have r ₂ relaxivity values comparable to traditional iron oxide nanoparticle contrast agents, and provide strong MR contrast when loaded into cells and implanted in tissue.

     

Rate of bacterial eradication by ophthalmic solutions of fourth-generation fluoroquinolones

Introduction

Antibacterial activity of ophthalmic fourth-generation fluoroquinolones has traditionally been evaluated by comparing only their active ingredients, gatifloxacin and moxifloxacin. However, ophthalmic formulations of fourth-generation fluoroquinolones differ in terms of the inclusion of preservatives. While gatifloxacin ophthalmic solution 0.3% (Zymar®; Allergan, Inc., Irvine, CA, USA) contains 0.005% benzalkonium chloride (BAK), moxifloxacin ophthalmic solution 0.5% (Vigamox®; Alcon Laboratories, Inc., Fort Worth, TX, USA) is preservative-free. Recent studies have demonstrated that the presence of BAK dramatically affects the antibacterial activity of the ophthalmic formulation of gatifloxacin. This study was designed to compare the kill rates of ophthalmic solutions of fourth-generation fluoroquinolones against isolates of common ocular bacterial pathogens.

Methods

Approximately 5.6 log₁₀ colony-forming units (CFU)/mL of Haemophilus influenzae (n=1), Streptococcus pneumoniae (n=1), Staphylococcus aureus (n=2), methicillin-resistant Staphylococcus aureus (MRSA) (n=4), methicillinresistant Staphylococcus epidermidis (MRSE) (n=4), and fluoroquinolone-resistant S. epidermidis (n=1) were incubated with ophthalmic solutions of either gatifloxacin or moxifloxacin. Viable bacteria were quantified at specific time points up to 60 minutes.

Results

Gatifloxacin 0.3% completely eradicated H. influenzae and Strep. pneumoniae in 5 minutes, one of two S. aureus isolates in 15 minutes, and the other S. aureus isolate in 60 minutes. Gatifloxacin 0.3% completely killed all MRSA, MRSE, and fluoroquinolone-resistant S. epidermidis isolates in 15 minutes. Moxifloxacin 0.5% completely eradicated Strep. pneumoniae and one of four MRSA isolates in 60 minutes. All other isolates incubated with moxifloxacin 0.5% retained viable bacteria ranging from 1.8 to 4.4 log₁₀ CFU/mL.

Conclusions

The ophthalmic solution of gatifloxacin 0.3% eradicated bacteria that frequently cause postoperative ocular infections substantially faster than did the ophthalmic solution of moxifloxacin 0.5%.

     

Synthesis and <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of [<Superscript>3</Superscript>H]LRRK2-IN-1 as a Novel Radioligand for LRRK2

Purpose

LRRK2 (leucine-rich repeat kinase 2) has recently been proven to be a promising drug target for Parkinson’s disease (PD) due to an apparent enhanced activity caused by mutations associated with familial PD. To date, there have been no reports in which a LRRK2 inhibitor has been radiolabeled and used for in in vitro or in vivo studies of LRRK2. In the present study, we radiolabeled the LRRK2 ligand, LRRK-IN-1, for the purposes of performing in vitro (IC₅₀, K _d , B _max, autoradiography) and in vivo (biodistribution, and blocking experiments) evaluations in rodents and human striatum tissues.

Procedures

[³H]LRRK2-IN-1 was prepared with high radiochemical purity (>99 %) and a specific activity of 41 Ci/mmol via tritium/hydrogen (T/H) exchange using Crabtree’s catalyst. For IC⁵⁰, K _d , and B _max determination, LRRK2-IN-1 was used as a competing drug for nonspecific binding assessment. The specific binding of the tracer was further evaluated via an in vivo blocking study in mice with a potent LRRK2 inhibitor, Pf-06447475.

Results

In vitro binding studies demonstrated a saturable binding site for [³H]LRRK2-IN-1 in rat kidney, rat brain striatum and human brain striatum with K _d of 26 ± 3 and 43 ± 8, 48 ± 2 nM, respectively. In rat, the density of LRRK2 binding sites (B _max) was higher in kidney (6.4 ± 0.04 pmol/mg) than in brain (2.5 ± 0.03 pmol/mg), however, in human brain striatum, the B _max was 0.73 ± 0.01 pmol/mg protein. Autoradiography imaging in striatum of rat and human brain tissues gave results consistent with binding studies. In in vivo biodistribution and blocking studies in mice, co-administration with Pf-06447475 (10 mg/kg) reduced the uptake of [³H]LRRK2-IN-1 (%ID/g) by 50–60% in the kidney or brain.

Conclusion

The high LRRK2 brain density observed in our study suggests the feasibility for positron emission tomography imaging of LRRK2 (a potential target) with radioligands of higher affinity and specificity.

     

How to not miss alveolar echinococcosis in hepatic lesions suspicious for cholangiocellular carcinoma

Purpose

Hepatic alveolar echinococcosis (AE) resembles intrahepatic cholangiocarcinoma (ICC) on radiological imaging. The purpose of this study was to identify criteria to discriminate AE from ICC with CT and MR Imaging.

Methods

One hundred and sixteen imaging studies of 94 patients (CT n = 65; MRI n = 51) diagnosed with AE (n = 55) or ICC (n = 39) were retrospectively reviewed by two blinded radiologists for lesion features including enhancement pattern and matrix composition. A consensus read was conducted in cases of disagreement. Uni- and multivariate logistic regression with bootstrapping were used for analysis.

Results

Using CT, no or septal enhancement and calcification yielded the highest values of sensitivity/specificity (90.9%/90.6% and 81.8%/96.9%) for AE. Using MRI, no or septal enhancement and cystic components achieved the highest sensitivity/specificity (90.9%/100.0% and 84.8%/66.7%) for AE. Multivariate logistic regression identified the following strong independent predictors for AE: for MRI, no or septal enhancement (odds ratio [OR] 322.4; p < 0.001); for CT, no or septal enhancement and calcification (OR 35.9 and 42.5; p < 0.001 and p < 0.01, respectively). No or septal enhancement and calcification demonstrated the highest interreader agreement (>90%).

Conclusion

Enhancement characteristics and matrix calcifications offer the strongest discriminating potential between AE and ICC with a high sensitivity, specificity, and interreader agreement.

     

Effects of Tiotropium Combined with Theophylline on Stable COPD Patients of Group B,D and its Impact on Small Airway Function: A Randomized Controlled Trial

Introduction

Tiotropium bromide has been widely used in clinical practice, while theophylline is another treatment option for chronic obstructive pulmonary disease (COPD). However, only a few relevant studies have investigated the long-term outcomes and efficacy of both in patients with COPD. We evaluated the effects of tiotropium and low-dose theophylline on stable COPD patients of groups B and D.

Methods

Eligible participants (n?=?170) were randomized and received either tiotropium 18 µg once daily with theophylline 100 mg twice daily (Group I) or tiotropium 18 µg once daily (Group II) for 6 months. COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scores and pulmonary function tests were measured before randomization and during the treatment.

Results

After 6 months of treatment, the CAT scores in both groups decreased significantly (11.41?±?3.56 and 11.08?±?3.05, p?<?0.0001). The changes of CAT (p?=?0.028) and mMRC scores (p?=?0.049) between the two groups differed after 1 month of treatment. In Group I, forced expiratory flow after 25% of the FVC% predicted (MEF₂₅% pred) was significantly improved after 3 months (4.84?±?8.73%, p?<?0.0001) and 6 months (6.21?±?8.65%, p?<?0.0001). There was a significant difference in small airway function tests (MEF₅₀% pred, MEF₂₅% pred, and MMEF% pred) between the two groups after 6 month of treatment (p?=?0.003, p?<?0.0001, and p?=?0.021, respectively).

Conclusions

Tiotropium combined with low-dose theophylline significantly improved the symptoms and general health of patients with stable COPD of groups B and D after 6 months of follow-up. Additionally, this therapy also improved the indicators of small airway function.

Trial Registration

Chinese Clinical Trial Registry (Registry ID: ChiCTR1800019027).

     

Comparison of the use of comprehensive point-of-care test panel to conventional laboratory process in emergency department

Background

In this study, we hypothesized that point of care testing (POCT) would reduce length of stay (LOS) in emergency department (ED) when compared to central laboratory testing and be a factor in patient discharge destination.

Methods

A single centre observational study was performed in ED non-ambulatory patients. Blood testing was performed either with POC instruments for blood gases and chemistry panel, full blood count, and CRP, or at central laboratory, or as a combination of both. Blood draw and POCTs were performed by experienced nurses.

Results

During the 4-week study period, 1759 patients underwent sample testing (POCT: n =?160, central lab: n =?951; both n =?648). Median waiting time for blood sampling was 19?min less in POCT than central laboratory (0:52 (95% confidence interval (CI) 0:46–1:02) vs. 1:11 (95% CI 1:05–1:14), p <?0.001). POCT results were available faster in both discharge groups, as expected. When imaging was not required, patients in POCT group were discharged home 55?min faster (4:57 (95% CI 3:59–6:17) vs. 5:52 (95% CI 5:21–6:35), p =?0.012) and 1?h 22?min faster when imaging was performed (5:48 (95% CI 5:26–6:18) vs. 7:10 (95% CI 6:47–8:26), p =?0.010). Similar reduction in sampling time and LOS was not seen among those admitted to hospital.

Conclusions

POCT shortened the laboratory process and made results available faster than the central lab. This allowed patients to be discharged home quicker. Thus, with proper training and education of the ED care team, POCT can be used as an effective tool for improving patient flow.

     

Determination of right ventricular ejection fraction by thermodilution technique — a comparison to biplane cineventriculography

Determination of right ventricular ejection fraction (RVEF) provides information about global right ventricular function, which may be important for the management of patients with various heart diseases. Right ventricular ejection fraction can be determined by new thermodilution techniques using fastresponse thermistors. To evaluate the validity of these methods, thermodilution measurements were compared with biplane cineventriculography in 22 patients undergoing cardiac catheterization. In all patients standard deviation of RVEF was below 5%. Mean RVEF, determined by thermodilution, was 52%±9%, ranging from 32% to 71% and correlated significantly with the results of angiography (RVEF: 52%±9%) (r=0.80, SEE±5%, n=22, p>0.001). Correlation was good especially in patients with small right ventricles (>60ml) (r=0.91, SEE±5%, n=13, p>0.001), lower heart rates (>65/min) (r=0.84, SEE=±6%, n=12, p>0.001) and cardiac output below 5.5 l/min (r=0.88, SEE±6%, n=11, p>0.001). Thus, if valid catheter placement is possible, right ventricular ejection fraction can be determined by thermodilution technique with good reproducibility and sufficient accuracy compared to biplane angio. Validation of this method in larger patient populations with various heart diseases is necessary.     

Superselective transcatheter arterial embolization in patients with acute peripancreatic bleeding complications: review of 44 cases

Purpose

To evaluate the efficacy of superselective transcatheter arterial embolization (TAE) in the treatment of acute peripancreatic bleeding complications.

Methods

During a 9-year period, 44 patients with acute bleeding of the peripancreatic arteries underwent TAE in our institution. Thirty-eight patients were treated using microcatheters and 6 patients with a diagnostic catheter. Embolic agents included coils (n = 38), polyvinyl alcohol (PVA) particles (n = 2), isobutyl cyanoacrylate (n = 2), coils plus PVA particles (n = 1), and coils plus isobutyl cyanoacrylate (n = 1). Outcome measures included technical success, clinical success, and the rate of complications.

Results

Identified bleeding sources included gastroduodenal artery (n = 14), splenic artery (n = 9), pancreaticoduodenal artery (n = 6), common hepatic artery (n = 5), superior mesenteric artery branches (n = 4), proper hepatic artery (n = 3), and dorsal/transverse pancreatic artery (n = 3). Technical success with effective control of active bleeding was achieved in 41/44 patients (93 %). Clinical success attributed to TAE alone was documented in 40/44 patients (91 %). The rate of major complications was 2 % including death in one patient.

Conclusions

Superselective TAE allows effective, minimally invasive control of acute peripancreatic bleeding complications with a low rate of therapeutically relevant complications.

     

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.     

Detection of <Emphasis Type="Italic">Klebsiella. Pneumoniae</Emphasis> Infection with an Antisense Oligomer Against its Ribosomal RNA

Purpose

Previously, we demonstrated specific accumulation into bacteria of a 12-mer phosphorodiamidate morpholino (MORF) oligomer complementary to a ribosomal RNA (rRNA) segment found in all bacteria using the universal probe called Eub338 (Eub). Here, two MORF oligomers Eco and Kpn with sequences specific to the rRNA of Escherichia coli (Eco) and Klebsiella pneumoniae (Kpn) were investigated along with Eub and control (nonEub).

Procedures

To determine bacterial rRNA binding, oligomers were tagged with Alexa Fluor 633 (AF633) for fluorescence in situ hybridization (FISH) and fluorescence microscopy, and radiolabeled with technetium-99m (Tc-99m) for biodistribution and SPECT imaging in infected mice.

Results

By both FISH and fluorescence microscopy, Eub showed a positive signal in both E. coli and K. pneumoniae as expected, and Kpn showed significantly higher accumulation in K. pneumoniae with near background in E. coli (p?<?0.01). Conversely, Eco was positive in both E. coli and K. pneumoniae, hence nonspecific. As determined by biodistribution, the accumulation of [^99mTc]Kpn was higher in the thigh infected with live K. pneumoniae than with live E. coli (p?=?0.05), and significantly higher than with heat-killed K. pneumoniae (p?=?0.02) in the target thigh. By SPECT imaging, the accumulation of [^99mTc]Kpn was obviously higher in its specific target of K. pneumoniae compared to an E. coli infected thigh.

Conclusions

Kpn complementary to the rRNA of K. pneumoniae, labeled with Tc-99m or AF633, demonstrated specific binding to fixed and live K. pneumoniae in culture and in infected mice such that Tc-99m-labeled Kpn as the MORF oligomer may be useful for K. pneumoniae infection detection through imaging.

     

Histogram analysis of noncancerous liver parenchyma on gadoxetic acid-enhanced MRI: predictive value for liver function and pathology

Purpose

To clarify whether the heterogeneity of hepatic parenchyma in the hepatobiliary phase on gadoxetic acid-magnetic resonance (MR) imaging is correlated with liver damage.

Materials and methods

We retrospectively examined the cases of 98 patients with or without chronic liver disease who underwent gadoxetic acid-enhanced 3T MR imaging before a hepatectomy between December 2010 and October 2014. For the evaluation of the heterogeneity of the signal intensity in the hepatobiliary phase, we placed the region of interest on the hepatic parenchyma, and the skewness and kurtosis were calculated using ImageJ software. A discriminant analysis was performed to examine the routine preoperative laboratory test results including indocyanine green retention at 15 min (ICG-R15), necro-inflammation grade, and liver fibrosis stage according to the METAVIR system: A0/1 (n = 69) and A2 (n = 29); F0/1 (n = 47), F2/3 (n = 31), and F4 (n = 20).

Results

The combination of skewness and kurtosis could discriminate the high ICG-R15 (>20) and low (<20) groups (lambda; 0.925, p = 0.025), necro-inflammatory grade (lambda; 0.926, p = 0.026), and fibrosis stage (lambda; 0.752, p < 0.0001) with statistical significance. The difference between the patients with normal values and those with an abnormal platelet count or aspartate transaminase level was also detectable (lambda; 0.901, p < 0.007, and lambda; 0.864, p = 0.001, respectively).

Conclusion

Histogram analyses of the hepatobiliary phase of gadoxetic acid-enhanced MR imaging have potential as a biomarker for the assessment of liver function, liver fibrosis, and necro-inflammation.

     

CT imaging of early local recurrence of pancreatic adenocarcinoma following pancreaticoduodenectomy

Purpose

The objectives of this retrospective study were to describe the characteristics and topography of pancreatic ductal adenocarcinoma and its early local recurrence after pancreaticoduodenectomy and identify predictive factors of local early recurrence by imaging computed tomography (CT).

Methods

The institutional review board approved the study and did require additional informed consent for reviewing the patients’ medical records and images. Patients who underwent pancreaticoduodenectomy for ductal adenocarcinoma, a preoperative CT scan, and adequate postoperative CT were included. After postoperative imaging, correlations among clinical and histological characteristics and preoperative imaging were evaluated.

Results

Among the 123 patients who underwent pancreaticoduodenectomy, 48 patients had sufficient follow-up imaging and were included in this study. A total of 33 patients experienced local early recurrence (Group 1), and 15 exhibited no local recurrence (Group 2). Local recurrence consisted of two types of anomalies: tissue nodules on surgical clips (94 %) and peri-arterial encasement (82 %). On preoperative imaging, the tumor diameter (p = 0.02) and the presence of a venous borderline resectable tumor (p < 0.0001) were predictive of local recurrence.

Conclusions

Tissue nodules on surgical clips and arterial encasement characterize early local recurrence, and nodules and encasement should not be considered common post-operative infiltration. The role of the radiologist is essential to assess the predictive factors of recurrence and to identify early local recurrence.

     

Bioluminescence Imaging of Colonization and Clearance Dynamics of <Emphasis Type="Italic">Brucella Suis</Emphasis> Vaccine Strain S2 in Mice and Guinea Pigs

Purpose

The goal of this study was to develop a plasmid-based lux bio-reporter for use to obtain in vivo images of Brucella suis vaccine strain 2 (B.suis S2) infection with high resolution and good definition.

Procedures

The pBBR-lux (pBBR1MCS-2-lxCDABE) plasmid that carries the luxCDABE operon was introduced into B. suis S2 by electroporation yielding B. suis S2-lux. The spatial and temporal transit of B. suis S2 in mice and guinea pigs was monitored by bioluminescence imaging.

Results

The plasmid pBBR-lux is stable in vivo and does not appear to impact the virulence or growth of bacteria. This sensitive luciferase reporter could represent B. suis S2 survival in real time. B. suis S2 mainly colonized the lungs, liver, spleen, and uterus in mice and guinea pigs as demonstrated by bioluminescence imaging.

Conclusion

The plasmid-based lux bioreporter strategy can be used to obtain high resolution in vivo images of B. suis S2 infection in mice and guinea pigs.

     

Morphological,Pathogenic and Molecular Characterizations of <Emphasis Type="Italic">Alternaria</Emphasis> Species Causing Early Blight of Tomato in Northern India

Early blight disease samples were collected from six different states of India. Seventeen different isolates of Alternaria spp were obtained in pure culture which were designated as PB-2, PB-4, PB-13, PB-17, PB-19, HR-12, HR-44, HR-62, MP-6, MP-7, JT-4, JT-11, UP-7, UP-10, UP-15, UP-20 and RJ-T-1. Characterization based on culture colour and conidial dimensions (conidial length and breadth, and beak length) indicated that no distinguished variation of the isolates was observed on the colour parameters. Although, a wide variation was observed in the length of conidia and beak, no significant difference was observed in conidial breadth except RJ-T-1. Among the isolates, conidial length of five isolates viz., HR-12, UP-7, UP-10, UP-15 and RJ-T-1 ranged from 80 to 97 µm whereas others were of significantly lesser size (30–51 µm). Similarly, significant difference was observed in beak length. The PCR amplification of the fungal DNA using universal primers ITS1 and ITS4 and sequencing indicated that, out of 17 isolates, 12 (JT-4, JT-11, HR-62, HR-44, PB-2, PB-4, PB-13, PB-17, PB-19, UP-20, MP-6 and MP-7) were closely matching with A. alternata (JX993756) and five isolates (HR-12, UP-7, UP-10, UP-15 and RJ-T-1) with A. solani (JF796068). Further, pathogenicity test on tomato revealed that both A. alternata and A. solani isolates were of virulent category indicating that former is also an incitant of early blight in northern India.     

Selecting Tumor-Specific Molecular Targets in Pancreatic Adenocarcinoma: Paving the Way for Image-Guided Pancreatic Surgery

Purpose

The purpose of this study was to identify suitable molecular targets for tumor-specific imaging of pancreatic adenocarcinoma.

Procedures

The expression of eight potential imaging targets was assessed by the target selection criteria (TASC)—score and immunohistochemical analysis in normal pancreatic tissue (n?=?9), pancreatic (n?=?137), and periampullary (n?=?28) adenocarcinoma.

Results

Integrin α_vβ₆, carcinoembryonic antigen (CEA), epithelial growth factor receptor (EGFR), and urokinase plasminogen activator receptor (uPAR) showed a significantly higher (all p?<?0.001) expression in pancreatic adenocarcinoma compared to normal pancreatic tissue and were confirmed by the TASC score as promising imaging targets. Furthermore, these biomarkers were expressed in respectively 88 %, 71 %, 69 %, and 67 % of the pancreatic adenocarcinoma patients.

Conclusions

The results of this study show that integrin α_vβ₆, CEA, EGFR, and uPAR are suitable targets for tumor-specific imaging of pancreatic adenocarcinoma.

     

Glucose Metabolism as a Pre-clinical Biomarker for the Golden Retriever Model of Duchenne Muscular Dystrophy

Purpose

Metabolic dysfunction in Duchenne muscular dystrophy (DMD) is characterized by reduced glycolytic and oxidative enzymes, decreased and abnormal mitochondria, decreased ATP, and increased oxidative stress. We analyzed glucose metabolism as a potential disease biomarker in the genetically homologous golden retriever muscular dystrophy (GRMD) dog with molecular, biochemical, and in vivo imaging.

Procedures

Pelvic limb skeletal muscle and left ventricle tissue from the heart were analyzed by mRNA profiling, qPCR, western blotting, and immunofluorescence microscopy for the primary glucose transporter (GLUT4). Physiologic glucose handling was measured by fasting glucose tolerance test (GTT), insulin levels, and skeletal and cardiac positron emission tomography/X-ray computed tomography (PET/CT) using the glucose analog 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG).

Results

MRNA profiles showed decreased GLUT4 in the cranial sartorius (CS), vastus lateralis (VL), and long digital extensor (LDE) of GRMD vs. normal dogs. QPCR confirmed GLUT4 downregulation but increased hexokinase-1. GLUT4 protein levels were not different in the CS, VL, or left ventricle but increased in the LDE of GRMD vs. normal. Microscopy revealed diffuse membrane expression of GLUT4 in GRMD skeletal but not cardiac muscle. GTT showed higher basal glucose and insulin in GRMD but rapid tissue glucose uptake at 5 min post-dextrose injection in GRMD vs. normal/carrier dogs. PET/ CT with [¹⁸F]FDG and simultaneous insulin stimulation showed a significant increase (p?=?0.03) in mean standard uptake values (SUV) in GRMD skeletal muscle but not pelvic fat at 5 min post-[¹⁸F]FDG /insulin injection. Conversely, mean cardiac SUV was lower in GRMD than carrier/normal (p?<?0.01).

Conclusions

Altered glucose metabolism in skeletal and cardiac muscle of GRMD dogs can be monitored with molecular, biochemical, and in vivo imaging studies and potentially utilized as a biomarker for disease progression and therapeutic response.