Expanding unilateral cochlear implantation criteria for adults with bilateral acquired severe sensorineural hearing loss

Abstract

Objectives

To report on a retrospective cohort study on the effects of expanding inclusion criteria for application of cochlear implants (CIs) on the performance 1-year post-implantation.

Methods

Based on pre-implantation audiometric thresholds and aided speech recognition scores, the data of 164 CI recipients were divided into a group of patients that fulfilled conservative criteria (mean hearing loss at 0.5, 1 and 2 kHz > 85 dB HL and phoneme scores with hearing aids < 30%), and the remaining group of patients that felt outside this conservative criterion. Speech recognition scores (in quiet) and quality of life (using the NCIQ) of both groups, measured at 1-year post-implantation, were compared.

Results

The group that felt outside the conservative criterion showed a higher phoneme score at 1-year post-implantation compared to the conservative group, suggesting that relaxed criteria have a positive influence on the speech recognition results with CI. With respect to quality of life, both groups significantly improved 1-year post-implantation. The conservative group showed a higher benefit on the advanced perception domain of the NCIQ. Based on their worse pre-implantation hearing, this was expected.

Conclusions

The data suggest that relaxation of CI indication positively affects the speech recognition performance of patients with severe hearing loss. Both groups of patients showed a positive effect of CI on the quality of life. This benefit relates to communication skills and the subjective day-to-day functioning in society.

https://ift.tt/2ViMVCQ

Inverse association between statin use and head and neck cancer: A population‐based case‐control study in Han population

Abstract

Background

This case‐control study aimed to find the relationship between prior statin use and head and neck cancer occurrence using a large population‐based database.

Methods

This study used claims data from the Taiwan Longitudinal Health Insurance Database. We included 5515 patients with head and neck cancer as cases and 5515 propensity score‐matched patients without head and neck cancer as controls. Conditional logistic regressions were performed to investigate the relationship between head and neck cancer and prior statin exposure.

Results

Of the 11 030 total sampled patients, 16.95% had previously received prescriptions for statins. In addition, statin exposure was found in 15.99% of cases and 17.91% of controls. The logistic regression also revealed that the adjusted odds ratio of prior statin exposure for cases was 0.86 (95% confidence interval: 0.77‐0.95) compared to propensity score‐matched controls.

Conclusion

This study found an inverse association between statin usage and head and neck cancer occurrence.

https://ift.tt/2Nw6MvR

Positive pressure device treatment for Menière’s disease: an overview of the current evidence and a meta-analysis

Abstract

Objective

The objective was to critically assess the current evidence investigating the efficacy of using a positive pressure device in patients with definite or probable Menière's disease.

Methods

We performed a systematic literature search in MEDLINE, EMBASE and PsycINFO up to February 2018. We included both systematic reviews and primary literature [randomized controlled trials (RCTs)] investigating positive pressure treatment, in patients (≥ 18 years of age), with Menière's disease. We assessed the internal validity of systematic reviews using the AMSTAR tool and risk of bias of primary studies using the Cochrane Risk of bias tool. We performed a meta-analysis for each outcome based on the identified studies. The overall certainty of evidence for the outcomes was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE).

Results

The search for systematic reviews identified four relevant reviews. These all included the same four RCTs. An updated search identified one additional RCT. In total, five RCTs were included in the data synthesis. Our data synthesis showed no effect of positive pressure treatment on primary nor secondary outcomes. No serious adverse events were reported. The overall certainty of evidence ranged from very low to low, due to the serious risk of bias and imprecision.

Conclusion

The current available evidence does not support positive pressure device treatment in patients with Menière's disease. However, the limitations of the current literature hinder the possibility of any solid conclusion. There remains a need for randomized controlled trials of high quality to fully access the utility of this treatment.

https://ift.tt/2tCLSSy

Coblator-Assisted Endoscopic Transnasal Resection of a Large Nasopharyngeal Pleomorphic Adenoma

Background. Pleomorphic adenomas occurring in the adult nasopharynx are rare, with our literature search identifying only 11 previous English-language reports. We document the unusual case of a large nasopharyngeal pleomorphic adenoma that was resected using radiofrequency coblation via an endoscopic transnasal approach. Methods. A 39-year-old male presented with worsening nasal congestion, intermittent otalgia, and a progressive change in voice. Flexible nasendoscopy showed a large homogeneous mass occupying the postnasal space, and computed tomography confirmed a 28 × 31 × 22 mm nasopharyngeal tumour. The biopsy-proven benign tumour was locally dissected using a coblator-assisted transnasal approach. Results. Histology confirmed complete excision of a myoepithelial-rich pleomorphic adenoma. The patient was symptom-free postoperatively, and no signs of recurrence were seen at one-year follow-up. Conclusions. This is a useful addition to the existing literature on surgical procedures used to treat benign pathology in the nasopharynx. The minimally invasive technique was well tolerated and had favourable patient outcomes.

https://ift.tt/2T4r5GO

Effects of septorhinoplasty on smell perception

Abstract

Purpose

To assess whether significant changes in smell perception occur after septorhinoplasty, and evaluate whether septum deviation, allergic rhinitis, and surgical technique affect postoperative smell perception.

Methods

Thirty-four patients (> 18 years old) awaiting septorhinoplasty were included, while those with previous severe hyposmia or anosmia were excluded. The participants self-assessed their smell perception using a 100-mm visual analogue scale (VAS), where 0 mm indicated the inability to smell and 100 mm indicated normal smell perception. The University of Pennsylvania Smell Identification Test (UPSIT) was applied before the procedure, and 4 and 12 weeks after surgery.

Results

The UPSIT score showed no significant changes at 4 (p = 0.59; 95% CI − 0.35 to + 2) or 12 weeks (p = 0.16; 95% CI − 1.13 to + 0.66). A comparison of the VAS scores before and 4 weeks after surgery (p = 0.62; 95% CI − 0.63 to + 0.39) yielded similar results. However, the average VAS scores improved 12 weeks after surgery (p = 0.007; 95% CI + 0.22 to + 1.30). Olfactory function, measured using the UPSIT, was not influenced by open or closed surgical techniques (p ≥ 0.10), the presence or absence of rhinitis (p ≥ 0.15), or obstructive septum deviation (p ≥ 0.38). Twelve weeks after surgery, self-evaluated smell perception was better in patients who underwent a closed procedure rather than an open procedure (p = 0.006; 95% CI: −1.39 to −0.37).

Conclusion

A validated test demonstrates that septorhinoplasty does not compromise smell perception 4 and 12 weeks after surgery. However, it might improve smell perception by the self-report observation.

https://ift.tt/2BS9OG2

IMRT Combined With Toripalimab in Unresectable Locally Recurrent Nasopharyngeal Carcinoma.

Conditions:   Nasopharyngeal Carcinoma;   Nasopharyngeal Neoplasms;   Nasopharyngeal Diseases;   Head and Neck Neoplasm
Interventions:   Drug: Tolipalimab;   Radiation: Reirradiation
Sponsor:   Sun Yat-sen University
Not yet recruiting

https://ift.tt/2BSw7M2

Experimental Pain Reporting Accuracy and Clinical Post-operative Pain

Conditions:   Surgical Procedure, Unspecified;   Pain, Postoperative;   ENT Disease
Intervention:   Device: pain reporting accuracy
Sponsors:   Carmel Medical Center;   University of Haifa
Not yet recruiting

https://ift.tt/2UbDmpi

A Dose Escalation Study of PF‑06939999 in Participants With Advanced or Metastatic Solid Tumors.

Conditions:   Advanced Solid Tumors;   Metastatic Solid Tumors
Intervention:   Drug: PF-06939999
Sponsor:   Pfizer
Not yet recruiting

https://ift.tt/2BTUs45

Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck

Conditions:   Lip;   Oral Cavity Squamous Cell Carcinoma;   Pharynx;   Larynx;   Squamous Cell Carcinoma
Interventions:   Biological: Nivolumab;   Biological: IDO1 Inhibitor BMS-986205;   Procedure: Therapeutic Conventional Surgery;   Other: Questionnaire Administration
Sponsor:   Thomas Jefferson University
Not yet recruiting

https://ift.tt/2U8lcoj

Serial Epstein-Barr Virus DNA Surveillance in Nasopharyngeal Carcinoma Patients

Condition:   Nasopharyngeal Carcinoma
Intervention:   Diagnostic Test: Plasma EBV DNA
Sponsor:   Sun Yat-sen University
Not yet recruiting

https://ift.tt/2BTUokR

Study of TQB2450 in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck（R/M SCCHN）

Condition:   Squamous Cell Carcinoma of the Head and Neck
Interventions:   Drug: TQB2450+cisplatin or carboplatin + 5-Fluorouracil (5-FU);   Drug: placebo+cisplatin or carboplatin + 5-Fluorouracil (5-FU)
Sponsor:   Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Not yet recruiting

https://ift.tt/2U5q2ms

Experimental research on the therapeutic effect of MMR vaccine to juvenile-onset recurrent respiratory papillomatosis

Abstract

Objective

To evaluate the efficacy of MMR vaccine in the treatment of juvenile-onset recurrent respiratory papillomatosis as adjuvant therapy by experimental research.

Methods

Thirty-one children with RRP were enrolled and assigned randomly to intervention group or control group. Fifteen subjects in intervention group were treated with local application MMR vaccine on the lesion after surgery; sixteen subjects in the control group were treated with surgical excision alone. The quantity of virus of positive specimens was measured by fluorescence quantitative polymerase chain reaction.

Results

After treatment with MMR vaccine, viral load of intervention group was (9.56 ± 11.03) × 10⁸  copies/ml, that of control group was (22.01 ± 17.78) × 10⁸ copies/ml, and there was significant difference between the two groups (P = 0.040).

Conclusions

Local application MMR vaccine as adjuvant therapy can reduce HPV viral load significantly. It is suggested that the MMR vaccine may inhibit replication of HPV DNA, but the curative effect needs further confirmation.

https://ift.tt/2NsUT9S

Otorhinolaryngological manifestations and delayed diagnosis in Kawasaki Disease

Publication date: Available online 26 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): M. Rouault, A. Coudert, R. Hermann, Y. Gillet, E. Truy, S. Ayari-Khalfallah

Abstract

Objectives

Kawasaki disease (KD) is a febrile multisystemic vasculitis of unknown etiology whose coronary prognosis is improved by early diagnosis and management. The objective of this study was to describe ENT manifestations encountered and to look for a delayed diagnosis associated with these manifestations.

Methods

A retrospective descriptive single-center study was conducted in Lyon between January 2009 and December 2017. All children treated for Kawasaki disease were included in the study. Clinical, biological and cardiac ultrasound data were collected. According to the diagnosis made at the first medical visit, children were classified into two groups: diagnosis of ENT spectrum or non-ENT diagnosis. The diagnostic times were compared by a Student test.

Results

142 patients were included: 64 in the ENT diagnostic group, 78 in the non-ENT diagnostic group. When the initial diagnosis was of ENT spectrum, the diagnostic time of KD was significantly longer: 8.51 days vs 5.77 days - (p <0.01). The total duration of fever was also longer - 10.92 vs 8.32 days – (p = 0.013) - and the frequency of antibiotics intake more important - 92.2% vs 46.2% - (p <0.01). Four children underwent surgery in the ENT diagnostic group: two retro-pharyngeal abscesses, one paracentesis and one cervicectomy.

Conclusions

ENT manifestations are frequently at the forefront of KD and constitute a misleading clinical picture responsible for delayed diagnosis and potentially inappropriate medico-surgical management. It is necessary to provide more education to practitioners for earlier recognition of Kawasaki disease.

https://ift.tt/2To2wEd

Radiation Exposure during Videofluoroscopic Swallowing Studies in Young Children

Publication date: Available online 25 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Eun Jae Ko, In Young Sung, Kyoung Hyo Choi, Yong Gyu Kwon, Jisun Yoon, Taehoon Kim

Abstract

Objectives

Swallowing difficulties are best assessed by videofluoroscopic swallowing studies (VFSS). However, limiting radiation exposure is important, especially in young children. The purpose was to evaluate radiation dose in young children during VFSS, and to investigate factors associated with it.

Methods

Children with swallowing difficulty who underwent VFSS from February 2012 to July 2014 were recruited. Dose area product (DAP) and screening time were offered by the fluoroscopy machine, and effective dose was calculated from the DAP using a conversion coefficient published by the National Radiological Protection Board (NRPB-R262). The age, gender, height, weight, body mass index (BMI), body surface area (BSA), underlying disease of the subject children, and results of VFSS were investigated.

Results

In 89 children (mean age 1.57±2.17, 55 boys and 34 girls), mean effective dose was 0.29±0.20 mSv, mean DAP was 2.41±1.65 Gy cm², and mean screening time was 2.24±0.99 minutes. The effective dose correlated with the screening time (r=0.598, p<0.001), age (r=0.210, p=0.049), height (r=0.521, p<0.001), weight (r=0.461, p<0.001), and BSA (r=0.493, p<0.001). There was no such correlation with gender, BMI, underlying disease, or the results of VFSS.

Conclusion

s: The effective dose during VFSS (0.29 mSv) in young children, which is affected by screening time, age, and body size, is considerably lower than the pediatric radiation exposure limit of 1mSv per year. However more than 4 VFSS annually would exceed this limit. Our findings will help physicians to reduce the radiation exposure and provide a useful references for future pediatric VFSS guidelines.

https://ift.tt/2IDPLBb

Occlusal height difference between maxillary central and lateral incisors: should aesthetic perception influence bracket placement?

Abstract

Background

The aim of this study was to verify anecdotal evidence that the maxillary central-to-lateral occlusal height difference (OHD) of more than 0.5 mm is a feature displayed in the majority of media and to discuss its implications for individualized orthodontic treatment planning.

Methods

Photographs of smiling female models were collected from a variety of printed advertisements and allocated to 3 groups (n = 30 each): 1 dental, 2 fashion and 3 orthodontics. Group 4 used female patient images from orthodontic textbooks, assuming an OHD of 0.5 mm between maxillary central and lateral incisors. OHD was assessed by measuring the incisor height on the photographs and using average values to establish height differences.

Results

The average maxillary central-to-lateral incisor OHD differences were 1.39 mm (dental literature), 1.34 mm (fashion advertisements), 1.23 mm (orthodontics) and 0.62 mm (orthodontic textbooks) respectively. The differences between the advertisement groups were not significant (P >  0.05), but for orthodontic textbooks they were (P <  0.001).

Conclusions

Advertisers seem to prefer greater maxillary central-to-lateral OHD compared to commonly used bracket placement protocols. Therefore, discussing OHD at start of treatment is recommended; modification of commonly used bracket placement protocols may be helpful to achieve desired aesthetic outcome.

https://ift.tt/2BTh5W5

ICD-10-Symptom-Rating-Fragebogen zur Beurteilung psychischer Komorbiditäten bei Patienten mit chronischem Tinnitus

Zusammenfassung

Hintergrund

Psychische Komorbiditäten bei Tinnituspatienten sind häufig und ihre Diagnostik ist wichtig für Interventionen und Therapieerfolg. Hierbei ist die Auswahl geeigneter Fragebögen entscheidend. Ziel dieser Studie war es, das ICD-10-Symptom-Rating (ISR) für die Diagnostik psychologischer Komorbiditäten zu untersuchen.

Methode

In der vorliegende Studie wurden Tinnitusbelastung und psychische Komorbidität bei n = 311 Patienten mit chronischem Tinnitus untersucht, die eine 7‑tägige multimodale tinnitusspezifische Intensivtherapie absolvierten. Zur Messung der Tinnitusbelastung wurde die deutsche Version des Tinnitus-Fragebogens (TF) eingesetzt. Psychische Komorbidität wurde mit dem ISR (Gesamtbelastung, depressives Syndrom, Angstsyndrom, Zwangssyndrom, somatoformes Syndrom, Essstörungssyndrom), Perceived Stress Questionnaire (PSQ: Gesamtwert für subjektive Stressbelastung, „Anspannung", „Sorgen", „Freude" und „Anforderungen") sowie der Allgemeinen Depressionsskala (ADS) gemessen.

Ergebnisse

Bei 65 % der Patienten bestanden psychische Komorbiditäten. Die Gesamtwerte des TF, ISR, PSQ und ADS zeigten signifikante Verbesserungen nach der Therapie. Zu Beginn der Therapie fanden sich signifikante Korrelationen der eingesetzten Messinstrumente, d. h., die Tinnitusbelastung konnte durch ISR-Gesamtbelastung, -Zwangssyndrom und PSQ-Anspannung vorhergesagt werden. Nach der Therapie wurde die – nun verringerte – Tinnitusbelastung zusätzlich durch die ISR-Unterskalen „Depression" und „Esstörungssyndrom" vorhergesagt.

Schlussfolgerung

Der ISR ist zur Erfassung komorbider psychischer Belastung bei Patienten mit chronischem Tinnitus und zur Erfassung kurzfristiger Therapieeffekte geeignet. Bei der Therapie des chronischen Tinnitus sollten stressassoziierte Anspannung, depressives Erleben und dysfunktionales Coping, z. B. über maladaptives Essverhalten, berücksichtigt werden.

https://ift.tt/2EgX9wZ

Statistics make their “official entry” in the European Annals of Otorhinolaryngology Head & Neck Diseases

Publication date: Available online 26 February 2019

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): Q. Lisan, C. Martin, O. Laccourreye

https://ift.tt/2H7xg5P

Guidelines (short version) of the French Society of Otorhinolaryngology (SFORL) on cervical lymphatic malformation in adults and children: Diagnosis

Publication date: Available online 25 February 2019

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): J. Lerat, A. Bisdorff-Bresson, M. Borsic, C. Chopinet, V. Couloignier, N. Fakhry, P. Fayoux, F. Jegoux, A. Larralde, N. Leboulanger, R. Nicollas, S. Pondaven Letourmy, SFORL work group

Abstract

Objectives

The authors present the guidelines of the French Society of Otorhinolaryngology (SFORL) for the diagnosis of cervical lymphatic malformation in adults and children.

Methods

A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group, and finalized in a coordination meeting. Guidelines were graded A, B, C or expert opinion, by decreasing level of evidence.

Results

The SFORL recommends that complete ENT examination should be performed to identify lesions at high risk of complication or associated with poor prognosis. In case of diagnostic doubt, especially in latero-cervical or oral floor lesions, fine-needle aspiration cytology should be performed before therapeutic decision-making. One or more validated classifications should be used to assess treatment efficacy and monitor progression. The reliability of antenatal diagnosis should be ensured by associating MRI to ultrasound. In antenatal diagnosis, the locoregional extension of the cervical lymphatic malformation should be evaluated accurately for prognosis, and associated malformations should be screened for, to guide treatment options.

https://ift.tt/2tDZFIM

A systematic review of hearing and vestibular function in carriers of the Pro51Ser mutation in the COCH gene

Abstract

Background and objectives

The Pro51Ser (P51S) COCH mutation is characterized by a late-onset bilateral sensorineural hearing loss (SNHL) and progressive vestibular deterioration. The aim of this study was to carry out a systematic review of all reported hearing and vestibular function data in P51S COCH mutation carriers and its correlation with age.

Materials and methods

Scientific databases including Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ISI Web of Knowledge, and Web of Science were searched to accumulate information about hearing outcome and vestibular function. Eleven genotype–phenotype correlation studies of the P51S COCH variant were identified and analyzed.

Results

The SNHL starts at the age of 32.8 years. The Annual Threshold Deterioration is 3 decibel hearing loss (dB HL) per year (1–24 dB HL/year). Profound SNHL was observed at 76 years on average (60–84 years). 136 individual vestibular measurements were collected from 86 carriers. The onset of the vestibular dysfunction was estimated around 34 years (34–40 years), and vestibular deterioration rates were higher than those of the SNHL, with complete bilateral loss observed between 49 and 60 years.

Conclusion

Both audiometric and vestibular data were processed with much different methodologies and pre-symptomatic P51S carriers were systematically underrepresented. Further delineation of this correlation would benefit cross-sectional and longitudinal study involving all (pre-symptomatic and symptomatic) P51S carriers.

https://ift.tt/2IALHS1

Cost analysis of office-based transnasal esophagoscopy

Abstract

Purpose

Although office-based transnasal esophagoscopy has been investigated extensively, a cost analysis is still lacking. We performed a cost analysis combined with feasibility study for two diagnostic processes: patients with globus pharyngeus and/or dysphagia, and hypopharyngeal carcinoma.

Methods

Prospective cohort study.

Results

Forty-one procedures were performed, of which 35 were fully completed. The procedure was well tolerated with mild complaints such as nasal or pharyngeal pain and burping. Four complications occurred: two minor epistaxis and two vasovagal reactions. In patients with globus pharyngeus and/or dysphagia, transnasal esophagoscopy resulted in a cost saving of €94.43 (p 0.026) per procedure, compared to our regular diagnostic process. In patients with suspicion of hypopharyngeal carcinoma, cost savings were €831.41 (p 0.000) per case.

Conclusions

Cost analysis showed that office-based transnasal esophagoscopy can provide significant cost savings for the current standard of care. Furthermore, this procedure resulted in good patient acceptability and few complications.

https://ift.tt/2TkJAG4

Molecular Imaging, vol. 12

2. 3D Fusion Framework for Infarction and Angiogenesis Analysis in a Myocardial Infarct Minipig Model

   Xu Zhenzhen, PhD¹, Bo Tao, PhD, MD², Yu Li, MSc¹, Jun Zhang, PhD¹, Xiaochao Qu, PhD¹, Feng Cao, PhD², Jimin Liang, PhD¹
   Molecular Imaging, vol. 16, First Published May 11, 2017.
   Abstract

   Hide Preview

   Abstract

   The combination of different modality images can provide detailed and comprehensive information for the prognostic assessment and therapeutic strategy of patients with ischemic heart disease. In this study, a 3D fusion framework is designed to integrate coronary computed tomography (CT) angiography (CTA), 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]DG) positron emission tomography (PET)/CT, and [⁶⁸Ga]-1,4,7-triazacyclononane-1,4,7-triacetic acid-(Arg-Gly-Asp)2 ([⁶⁸Ga]-NOTA-PRGD2) PET/CT images of the myocardial infarction model in minipigs. First, the structural anatomy of the heart in coronary CTA and CT is segmented using a multi-atlas-based method. Then, the hearts are registered using the B-spline-based free form deformation. Finally, the [¹⁸F]DG and [⁶⁸Ga]-NOTA-PRGD2 signals are mapped into the heart in coronary CTA, which produces a single fusion image to delineate both the cardiac structural anatomy and the functional information of myocardial viability and angiogenesis. Heart segmentation demonstrates high accuracy with good agreement between manual delineation and automatic segmentation. The fusion result intuitively reflects the extent of the [¹⁸F]DG uptake defect as well as the location where the [⁶⁸Ga]-NOTA-PRGD2 signal appears. The fusion result verified the occurrence of angiogenesis based on the in vivo noninvasive molecular imaging approach. The presented framework is helpful in facilitating the study of the relationship between infarct territories and blocked coronary arteries as well as angiogenesis.
    
3. 

   Whole-Body Distribution of Leukemia and Functional Total Marrow Irradiation Based on FLT-PET and Dual-Energy CT

   Taiki Magome, PhD¹², Jerry Froelich, MD³, Shernan G. Holtan, MD⁴, Yutaka Takahashi, PhD²⁵, Michael R. Verneris, MD⁴, Keenan Brown, PhD⁶, Kathryn Dusenbery,MD⁷, Jeffrey Wong, MD⁸, Susanta K. Hui, PhD²⁷⁸
   Molecular Imaging, vol. 16, First Published September 26, 2017.
   Abstract

   Hide Preview

   Abstract

   This report describes a multimodal whole-body 3′-deoxy-3′[(18)F]-fluorothymidine positron emission tomography (FLT-PET) and dual-energy computed tomography (DECT) method to identify leukemia distribution within the bone marrow environment (BME) and to develop disease- and/or BME-specific radiation strategies. A control participant and a newly diagnosed patient with acute myeloid leukemia prior to induction chemotherapy were scanned with FLT-PET and DECT. The red marrow (RM) and yellow marrow (YM) of the BME were segmented from DECT using a basis material decomposition method. Functional total marrow irradiation (fTMI) treatment planning simulations were performed combining FLT-PET and DECT imaging to differentially target irradiation to the leukemia niche and the rest of the skeleton. Leukemia colonized both RM and YM regions, adheres to the cortical bone in the spine, and has enhanced activity in the proximal/distal femur, suggesting a potential association of leukemia with the BME. The planning target volume was reduced significantly in fTMI compared with conventional TMI. The dose to active disease (standardized uptake value >4) was increased by 2-fold, while maintaining doses to critical organs similar to those in conventional TMI. In conclusion, a hybrid system of functional–anatomical–physiological imaging can identify the spatial distribution of leukemia and will be useful to both help understand the leukemia niche and develop targeted radiation strategies.
    
4. 

   Vulnerable Plaque Detection and Quantification with Gold Particle–Enhanced Computed Tomography in Atherosclerotic Mouse Models

   David De Wilde, Bram Trachet, Carole Van der Donckt, Bert Vandeghinste, Benedicte Descamps, Christian Vanhove, Guido R. Y. De Meyer, Patrick Segers
   Molecular Imaging, vol. 14, 6, First Published June 1, 2015.
   Abstract

   Hide Preview

   Abstract

   Recently, an apolipoprotein E–deficient (ApoE^−/−) mouse model with a mutation (C1039G+/−) in the fibrillin-1 (Fbn1) gene (ApoE^−/−Fbn1^C1039G+/− mouse model) was developed showing vulnerable atherosclerotic plaques, prone to rupture, in contrast to the ApoE^−/− mouse model, where mainly stable plaques are present. One indicator of plaque vulnerability is the level of macrophage infiltration. Therefore, this study aimed to measure and quantify in vivo the macrophage infiltration related to plaque development and progression. For this purpose, 5-weekly consecutive gold nanoparticle–enhanced micro–computed tomography (microCT) scans were acquired. Histology confirmed that the presence of contrast agent coincided with the presence of macrophages. Based on the microCT scans, regions of the artery wall with contrast agent present were calculated and visualized in three dimensions. From this information, the contrast-enhanced area and contrast-enhanced centerline length were calculated for the branches of the carotid bifurcation (common, external, and internal carotid arteries). Statistical analysis showed a more rapid development and a larger extent of plaques in the ApoE^−/−Fbn1^C1039G+/− compared to the ApoE^−/−mice. Regional differences between the branches were also observable and quantifiable. We developed and applied a methodology based on gold particle–enhanced microCT to visualize the presence of macrophages in atherosclerotic plaques in vivo.
    
5. 

   Complementary Use of Bioluminescence Imaging and Contrast-Enhanced Micro—Computed Tomography in an Orthotopic Brain Tumor Model

   Sanaz Yahyanejad, Patrick V. Granton, Natasja G. Lieuwes, Lesley Gilmour, Ludwig Dubois, Jan Theys, Anthony J. Chalmers, Frank Verhaegen, Marc Vooijs
   Molecular Imaging, vol. 13, 4, First Published January 1, 2015.
   Abstract

   Hide Preview

   Abstract

   Small animal models are crucial to link molecular discoveries and implementation of clinically relevant therapeutics in oncology. Using these models requires noninvasive imaging techniques to monitor disease progression and therapy response. Micro–computed tomography (CT) is less studied for the in vivo monitoring of murine intracranial tumors and traditionally suffers from poor soft tissue contrast, whereas bioluminescence imaging (BLI) is known for its sensitivity but is not frequently employed for quantifying tumor volume. A widely used orthotopic glioblastoma multiforme (GBM) tumor model was applied in nude mice, and tumor growth was evaluated by BLI and contrast-enhanced microCT imaging. A strong correlation was observed between CT volume and BLI-integrated intensity (Pearson coefficient (r) = .85, p = .0002). Repeated contouring of contrast-enhanced microCT-delineated tumor volumes achieved an intraobserver average pairwise overlap ratio of 0.84 and an average tumor volume coefficient of variance of 0.11. MicroCT-delineated tumor size was found to correlate with tumor size obtained via histologic analysis (Pearson coefficient (r) = .88, p = .005). We conclude that BLI intensity can be used to derive tumor volume but that the use of both contrast-enhanced microCT and BLI provides complementary tumor growth information, which is particularly useful for modern small animal irradiation devices that make use of microCT and BLI for treatment planning, targeting, and monitoring.
    
6. 

   Development and Validation of a Complete GATE Model of the Siemens Inveon Trimodal Imaging Platform

   Sanghyeb Lee, Jens Gregor, Dustin Osborne
   Molecular Imaging, vol. 12, 7, First Published October 1, 2013.
   Abstract

   Hide Preview

   Abstract

   This article presents and validates a newly developed GATE model of the Siemens Inveon trimodal imaging platform. Fully incorporating the positron emission tomography (PET), single-photon emission computed tomography (SPECT), and computed tomography (CT) data acquisition subsystems, this model enables feasibility studies of new imaging applications, the development of reconstruction and correction algorithms, and the creation of a baseline against which experimental results for real data can be compared. Model validation was based on comparing simulation results against both empirical and published data. The PET modality was validated using the NEMA NU-4 standard. Validations of SPECT and CT modalities were based on assessment of model accuracy compared to published and empirical data on the platform. Validation results show good agreement between simulation and empirical data of approximately ± 5%.
    
7. 

   Use of eXIA 160 XL for Contrast Studies in Micro–Computed Tomography: Experimental Observations

   Inneke Willekens, Nico Buls, Michel De Maeseneer, Tony Lahoutte, Johan de Mey
   Molecular Imaging, vol. 12, 6, First Published September 1, 2013.
   Abstract

   Hide Preview

   Abstract

   The purpose of this study was to evaluate the time course of contrast enhancement of spleen, liver, and blood using eXIA 160 XL in healthy mice. eXIA 160 XL was intravenously injected in C57bl/6 mice (n = 12) at a dose of 0.1 mL/20 g (16 mg iodine [I]/20 g) (n = 6) or 0.2 mL/20 g (32 mg I/20 g) (n = 6). The distribution was analyzed by repeated micro–computed tomographic scans up to 48 hours after contrast administration. Images were analyzed using Amidesoftware. Regions of interest were drawn in the spleen, liver, and left ventricle. Contrast enhancement was measured and expressed as a function of time. Peak contrast enhancement of the spleen was reached at 30 minutes, and peak contrast enhancement of the liver occurred 45 minutes after 16 mg I/20 g. Given that this contrast was found to be rather low in the spleen in comparison with former eXIA 160 products, experiments were done at a higher dose. However, the 32 mg I/20 g dose was lethal for mice. Enhancement inside the heart lasts for 1 hour. Administration of eXIA 160 XL results in long-lasting blood pool contrast with higher contrast enhancement in heart and liver in comparison with eXIA 160; however, the administered dose should be limited to 16 mg I/20 g.
    
8. 

   Comparison of Computed Tomography– and Optical Image–Based Assessment of Liposome Distribution

   Huang Huang, Michael Dunne, John Lo, David A. Jaffray, Christine Allen
   Molecular Imaging, vol. 12, 3, First Published May 1, 2013.
   Abstract

   Hide Preview

   Abstract

   The use of multimodal imaging as a tool to assess the in vivo pharmacokinetics and biodistribution of nanocarriers is important in understanding the nature of their in vivo transport. The current study reports the development of a nano-sized liposomal computed tomographic (CT)/optical imaging probe carrying iohexol and Cy5.5 and its use in micro-CT and optical imaging to quantitatively assess the whole-body (macroscopic), intratumoral, and microscopic distribution over a period of 8 days. These multimodal liposomes have a vascular half-life of 30.3 ± 8.9 hours in mice bearing subcutaneous H520 non-small cell lung cancer tumors, with the maximum liposome accumulation in tumor achieved 48 hours postinjection. The in vivo liposome distribution and stability were quantitatively assessed using both micro-CT and fluorescence molecular tomography. The combination of CT and optical imaging enables visualization of the liposomes at the whole-body, tumor, and cellular scales with high sensitivity. Such noninvasive tracking of therapeutic vehicles at the macro- and microscale is important for informed and rational development of novel nanocarrier systems.
    

Molecular Imaging, vol. 13

2. Decreased Taurine and Creatine in the Thalamus May Relate to Behavioral Impairments in Ethanol-Fed Mice: A Pilot Study of Proton Magnetic Resonance Spectroscopy

   Su Xu, PhD¹, Wenjun Zhu, MS¹, Yamin Wan, MD, PhD¹², JiaBei Wang, PhD³, Xi Chen, PhD⁴, Liya Pi, PhD⁵, Mary Kay Lobo, PhD⁶, Bin Ren, PhD⁷, Zhekang Ying, PhD⁸,Michael Morris, MD¹, Qi Cao, MD, PhD¹
   Molecular Imaging, vol. 17, First Published January 10, 2018.
   Abstract

   Hide Preview

   Abstract

   Minimal hepatic encephalopathy (MHE) is highly prevalent, observed in up to 80% of patients with liver dysfunction. Minimal hepatic encephalopathy is defined as hepatic encephalopathy with cognitive deficits and no grossly evident neurologic abnormalities. Clinical management may be delayed due to the lack of in vivo quantitative methods needed to reveal changes in brain neurobiochemical biomarkers. To gain insight into the development of alcoholic liver disease–induced neurological dysfunction (NDF), a mouse model of late-stage alcoholic liver fibrosis (LALF) was used to investigate changes in neurochemical levels in the thalamus and hippocampus that relate to behavioral changes. Proton magnetic resonance spectroscopy of the brain and behavioral testing were performed to determine neurochemical alterations and their relationships to behavioral changes in LALF. Glutamine levels were higher in both the thalamus and hippocampus of alcohol-treated mice than in controls. Thalamic levels of taurine and creatine were significantly diminished and strongly correlated with alcohol-induced behavioral changes. Chronic long-term alcohol consumption gives rise to advanced liver fibrosis, neurochemical changes in the nuclei, and behavioral changes which may be linked to NDF. Magnetic resonance spectroscopy represents a sensitive and noninvasive measurement of pathological alterations in the brain, which may provide insight into the pathogenesis underlying the development of MHE.
    
3. 

   Magnetic Resonance Imaging for Characterization of a Chick Embryo Model of Cancer Cell Metastases

   Anne Herrmann, PhD¹, Arthur Taylor, PhD², Patricia Murray, PhD², Harish Poptani, PhD², Violaine Sée, PhD¹
   Molecular Imaging, vol. 17, First Published November 5, 2018.
   Abstract

   Hide Preview

   Abstract

   Metastasis is the most common cause of death for patients with cancer. To fully understand the steps involved in metastatic dissemination, in vivo models are required, of which murine ones are the most common. Therefore, preclinical imaging methods such as magnetic resonance imaging (MRI) have mainly been developed for small mammals and their potential to monitor cancer growth and metastasis in nonmammalian models is not fully harnessed. We have here used MRI to measure primary neuroblastoma tumor size and metastasis in a chick embryo model. We compared its sensitivity and accuracy to end-point fluorescence detection upon dissection. Human neuroblastoma cells labeled with green fluorescent protein (GFP) and micron-sized iron particles were implanted on the extraembryonic chorioallantoic membrane of the chick at E7. T₂ RARE, T₂-weighted fast low angle shot (FLASH) as well as time-of-flight MR angiography imaging were applied at E14. Micron-sized iron particle labeling of neuroblastoma cells allowed in ovo observation of the primary tumor and tumor volume measurement noninvasively. Moreover, T₂ weighted and FLASH imaging permitted the detection of small metastatic deposits in the chick embryo, thereby reinforcing the potential of this convenient, 3R compliant, in vivo model for cancer research.
    
4. 

   Image-Based Analysis of Tumor Localization After Intra-Arterial Delivery of Technetium-99m-Labeled SPIO Using SPECT/CT and MRI

   In Joon Lee, MD, PhD¹, Ji Yong Park, MS²³, Young-il Kim, MD, PhD²⁴, Yun-Sang Lee, PhD²⁴, Jae Min Jeong, PhD², Jaeil Kim, BS², Euishin Edmund Kim, MD, PhD⁴⁵,Keon Wook Kang, MD, PhD², Dong Soo Lee, MD, PhD²⁴, Seonji Jeong, MD⁶, Eun Jeong Kim, BS⁶, Young Il Kim, MD, PhD⁶⁷, Jin Wook Chung, MD, PhD⁶
   Molecular Imaging, vol. 16, First Published January 24, 2017.
   Abstract

   Hide Preview

   Abstract

   The aim of this study is to evaluate the localization of ^99mTc-labeled dextran-coated superparamagnetic iron oxide (SPIO) nanoparticles to the liver tumor using image-based analysis. We delivered ^99mTc-SPIO intravenously or intra-arterially (IA) with/without Lipiodol to compare the tumor localization by gamma scintigraphy, single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) in a rabbit liver tumor. The gamma and SPECT image-based analysis shows that the uptake ratio of the tumor to the normal liver parenchyma is highest after delivery of ^99mTc-SPIO with Lipiodol IA and that well correlates with the trend of the signal decrease in the liver MRIs. Intra-arterial delivery of SPIO with Lipiodol might be a good drug delivery system targeting the hepatic tumors, as confirmed by image-based analysis.
    
5. 

   Preclinical Multimodal Molecular Imaging Using ¹⁸F-FDG PET/CT and MRI in a Phase I Study of a Knee Osteoarthritis in In Vivo Canine Model

   Maria I. Menendez, DVM, PhD¹, Bianca Hettlich, DrMedVet¹², Lai Wei, PhD³, Michael V. Knopp, MD, PhD¹
   Molecular Imaging, vol. 16, First Published March 24, 2017.
   Abstract

   Hide Preview

   Abstract

   The aim of this study was to use a multimodal molecular imaging approach to serially assess regional metabolic changes in the knee in an in vivo anterior cruciate ligament transection (ACLT) canine model of osteoarthritis (OA). Five canine underwent ACLT in one knee and the contralateral knee served as uninjured control. Prior, 3, 6, and 12 weeks post-ACLT, the dogs underwent ¹⁸F-fluoro-d-glucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI). The MRI was coregistered with the PET/CT, and 3-dimensional regions of interest (ROIs) were traced manually and maximum standardized uptake values (SUV_max) were evaluated. ¹⁸F-fluoro-d-glucose SUV_max in the ACLT knee ROIs was significantly higher compared to the uninjured contralateral knees at 3, 6, and 12 weeks. Higher ¹⁸F-FDG uptake observed in ACLT knees compared to the uninjured knees reflects greater metabolic changes in the injured knees over time. Knee ¹⁸F-FDG uptake in an in vivo ACLT canine model using combined PET/CT and MRI demonstrated to be highly sensitive in the detection of metabolic alterations in osseous and nonosteochondral structures comprising the knee joint. ¹⁸F-fluoro-d-glucose appeared to be a capable potential imaging biomarker for early human knee OA diagnosis, prognosis, and management.
    
6. 

   Commentary on "A Microfluidic Platform to Design Crosslinked Hyaluronic Acid Nanoparticles (cHANPs) for Enhanced MRI"

   Maria Russo, PhD¹², Paolo Bevilacqua, PhD³, Paolo Antonio Netti, PhD¹²⁴, Enza Torino, PhD¹⁴
   Molecular Imaging, vol. 16, First Published May 15, 2017.
   Abstract

   Hide Preview

   Abstract

   Strategies to enhance the relaxometric properties of gadolinium (Gd)-based contrast agents (CAs) for magnetic resonance imaging (MRI), without the chemical modification of chelates, have recently had a strong impact on the diagnostic field. We have taken advantage of the interaction between Gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) and the hydrogel structure of hyaluronic acid to design cross-linked hyaluronic acid nanoparticles down to 35 nm for use in MRI applications. The proposed bioformulations enable the control of the relaxometric properties of CAs, thus boosting the relaxation rate of T1. Our results led us to identify this approach as an adjustable scenario to design intravascularly injectable hydrogel nanoparticles entrapping Gd-DTPA. This approach overcomes the general drawbacks of clinically approved CAs having poor relaxivity and toxic effects.
    
7. 

   Phosphatidylserine-Targeted Nanotheranostics for Brain Tumor Imaging and Therapeutic Potential

   Lulu Wang, MD, PhD¹, Amyn A. Habib, MD²³, Akiva Mintz, MD, PhD⁴⁵, King C. Li, MD⁴⁶, Dawen Zhao, MD, PhD¹³
   Molecular Imaging, vol. 16, First Published May 15, 2017.
   Abstract

   Hide Preview

   Abstract

   Phosphatidylserine (PS), the most abundant anionic phospholipid in cell membrane, is strictly confined to the inner leaflet in normal cells. However, this PS asymmetry is found disruptive in many tumor vascular endothelial cells. We discuss the underlying mechanisms for PS asymmetry maintenance in normal cells and its loss in tumor cells. The specificity of PS exposure in tumor vasculature but not normal blood vessels may establish it a useful biomarker for cancer molecular imaging. Indeed, utilizing PS-targeting antibodies, multiple imaging probes have been developed and multimodal imaging data have shown their high tumor-selective targeting in various cancers. There is a critical need for improved diagnosis and therapy for brain tumors. We have recently established PS-targeted nanoplatforms, aiming to enhance delivery of imaging contrast agents across the blood–brain barrier to facilitate imaging of brain tumors. Advantages of using the nanodelivery system, in particular, lipid-based nanocarriers, are discussed here. We also describe our recent research interest in developing PS-targeted nanotheranostics for potential image-guided drug delivery to treat brain tumors.
    
8. 

   Feasibility of Na¹⁸F PET/CT and MRI for Noninvasive In Vivo Quantification of Knee Pathophysiological Bone Metabolism in a Canine Model of Post-traumatic Osteoarthritis

   Maria I. Menendez, DVM, PhD¹, Bianca Hettlich, DrMedVet¹², Lai Wei, PhD³, Michael V. Knopp, MD, PhD¹
   Molecular Imaging, vol. 16, First Published July 21, 2017.
   Abstract

   Hide Preview

   Abstract

   Purpose:

   To assess and quantify by molecular imaging knee osseous metabolic changes serially in an in vivo canine model of posttraumatic osteoarthritis (PTOA) of the knee utilizing sodium fluoride (Na¹⁸F) positron emission tomography (PET)/computed tomography (CT) coregistered with magnetic resonance imaging (MRI).

   Materials and Methods:

   Sodium fluoride PET imaging of 5 canines was performed prior to anterior cruciate ligament transection (ACLT) and 2 times post-ACLT (3 and 12 weeks). The PET/CT was coregistered with MRI, enabling serial anatomically guided visual and quantitative three-dimensional (3D) region of interest (ROI) assessment by maximum standardized uptake value.

   Results:

   Prior to ACLT, every 3D ROI assessed in both knees showed no Na¹⁸F uptake above background. The uptake of Na¹⁸F in the bone of the ACLT knees increased exponentially, presenting significantly higher uptake at 12 weeks in every region compared to the ACLT knees at baseline. Furthermore, the uninjured contralateral limb and the ipsilateral distal bones and joints presented Na¹⁸F uptake at 3 and 12 weeks post-ACLT.

   Conclusion:

   This study demonstrated that Na¹⁸F PET/CT coregistered with MRI is a feasible molecular imaging biomarker to assess knee osseous metabolic changes serially in an in vivo canine model of knee PTOA. Moreover, it brings a novel musculoskeletal preclinical imaging methodology that can provide unique insights into PTOA pathophysiology.
    
9. 

   Rethinking Brain Cancer Therapy: Tumor Enzyme Activatable Theranostic Nanoparticles

   Heike E. Daldrup-Link, MD, PhD¹²³
   Molecular Imaging, vol. 16, First Published September 20, 2017.
   Abstract

   Hide Preview

   Abstract

   This invited commentary discusses a recent article by Mohanty et al in Molecular Cancer Therapeutics about significant therapeutic efficacies of novel theranostic nanoparticles (TNPs) for the treatment of human brain cancers in mouse models. The TNPs were cleaved by enzymes in the tumor tissue, matrix metalloproteinase (MMP-14), which lead to release of a highly potent therapeutic drug, azademethylcolchicine. Data showed that the TNPs caused selective toxic effects in MMP-14-expressing glioblastoma and not normal brain. In addition, the iron oxide nanoparticle backbone enabled in vivo drug tracking with magnetic resonance imaging (MRI). This commentary discusses previous efforts of MMP-targeted therapeutics as well as opportunities for further refinements of tumor enzyme-activatable TNPs. If successfully translated to clinical applications, the TNPs might hold substantial potential to improving cytotoxic indexes and long-term outcomes of patients with brain cancer compared to standard therapy.
    
10. 

    Labeling Human Melanoma Cells With SPIO: In Vitro Observations

    Daniel Spira, MD¹, Rüdiger Bantleon, PhD², Hartwig Wolburg, PhD³, Fritz Schick, MD, PhD⁴, Gerd Groezinger, MD², Jakub Wiskirchen, MD⁵, Benjamin Wiesinger,MD²
    Molecular Imaging, vol. 15, First Published January 29, 2016.
    Abstract

    Hide Preview

    Abstract

    Objectives:

    To use the superparamagnetic iron oxide (SPIO) contrast agent Resovist (±transfection agent) to label human melanoma cells and determine its effects on cellular viability, microstructure, iron quantity, and magnetic resonance imaging (MRI) detectability.

    Materials and Methods:

    Human SK-Mel28 melanoma cells were incubated with Resovist (±liposomal transfection agent DOSPER). The cellular iron content was measured, and labeled cells were examined at 1.5 T and 3.0 T. The intracellular and extracellular distributions of the contrast agent were assessed by light and electron microscopy.

    Results:

    The incubation of melanoma cells with SPIO does not interfere with cell viability or proliferation. The iron is located both intracellularly and extracellularly as iron clusters associated with the exterior of the cell membrane. Despite thorough washing, the extracellular SPIO remained associated with the cell membrane. The liposomal transfection agent does not change the maximum achievable cellular iron content but promotes a faster iron uptake. The MRI detectability persists for at least 7 days.

    Conclusion:

    The transfection agent DOSPER facilitates the efficient labeling of human metastatic melanoma cells with Resovist. Our findings raise the possibility that other Resovist-labeled cells may collect associated extracellular nanoparticles. The SPIO may be available to other iron-handling cells and not completely compartmentalized during the labeling procedure.
     
11. 

    MS-1 magA: Revisiting Its Efficacy as a Reporter Gene for MRI

    Sofia M. Pereira, PhD¹, Steve R. Williams, PhD², Patricia Murray, PhD¹, Arthur Taylor, PhD¹
    Molecular Imaging, vol. 15, First Published April 26, 2016.
    Abstract

    Hide Preview

    Abstract

    Bacterial genes involved in the biomineralization of magnetic nanoparticles in magnetotactic bacteria have recently been proposed as reporters for magnetic resonance imaging (MRI). In such systems, the expression of the bacterial genes in mammalian cells purportedly leads to greater concentrations of intracellular iron or the biomineralization of iron oxides, thus leading to an enhancement in relaxation rate that is detectable via MRI. Here, we show that the constitutive expression of the magA gene from Magnetospirillum magnetotacticum is tolerated by human embryonic kidney (HEK) cells but induces a strong toxic effect in murine mesenchymal/stromal cells and kidney-derived stem cells, severely restricting its effective use as a reporter gene for stem cells. Although it has been suggested that magA is involved in iron transport, when expressed in HEK cells, it does not affect the transcription of endogenous genes related to iron homeostasis. Furthermore, the magA-induced enhancement in iron uptake in HEK cells is insignificant, suggesting this gene is a poor reporter even for cell types that can tolerate its expression. We suggest that the use of magA for stem cells should be approached with caution, and its efficacy as a reporter gene requires a careful assessment on a cell-by-cell basis.
     
12. 

    Assessing Metabolic Changes in Response to mTOR Inhibition in a Mantle Cell Lymphoma Xenograft Model Using AcidoCEST MRI

    Paul J. Akhenblit, PhD¹, Neale T. Hanke, PhD², Alexander Gill, BS², Daniel O. Persky, MD², Christine M. Howison, MS³, Mark D. Pagel, PhD¹²³, Amanda F. Baker,PharmD, PhD²
    Molecular Imaging, vol. 15, First Published May 2, 2016.
    Abstract

    Hide Preview

    Abstract

    AcidoCEST magnetic resonance imaging (MRI) has previously been shown to measure tumor extracellular pH (pHe) with excellent accuracy and precision. This study investigated the ability of acidoCEST MRI to monitor changes in tumor pHe in response to therapy. To perform this study, we used the Granta 519 human mantle cell lymphoma cell line, which is an aggressive B-cell malignancy that demonstrates activation of the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway. We performed in vitro and in vivo studies using the Granta 519 cell line to investigate the efficacy and associated changes induced by the mTOR inhibitor, everolimus (RAD001). AcidoCEST MRI studies showed a statistically significant increase in tumor pHe of 0.10 pH unit within 1 day of initiating treatment, which foreshadowed a decrease in tumor growth of the Granta 519 xenograft model. AcidoCEST MRI then measured a decrease in tumor pHe 7 days after initiating treatment, which foreshadowed a return to normal tumor growth rate. Therefore, this study is a strong example that acidoCEST MRI can be used to measure tumor pHe that may serve as a marker for therapeutic efficacy of anticancer therapies.
     
13. 

    Investigating the Relationship between Transverse Relaxation Rate (R2) and Interecho Time in MagA-Expressing, Iron-Labeled Cells

    Casey Y. Lee, R. Terry Thompson, Frank S. Prato, Donna E. Goldhawk, Neil Gelman
    Molecular Imaging, vol. 14, 12, First Published December 1, 2015.
    Abstract

    Hide Preview

    Abstract

    Reporter gene–based labeling of cells with iron is an emerging method of providing magnetic resonance imaging contrast for long-term cell tracking and monitoring cellular activities. This report investigates 9.4 T nuclear magnetic resonance properties of mammalian cells overexpressing MagA, a putative iron transport protein from magnetotactic bacteria. MagA-expressing MDA-MB-435 cells were cultured in the presence and absence of iron supplementation and compared to the untransfected control. The relationship between the transverse relaxation rate (R2) and interecho time was investigated using the Carr-Purcell-Meiboom-Gill sequence. This relationship was analyzed using a model based on water diffusion in weak magnetic field inhomogeneities (Jensen-Chandra model) as well as a fast-exchange model (Luz-Meiboom model). Increases in R2 with increasing interecho time were larger in the iron-supplemented, MagA-expressing cells compared to other cells. The dependence of R2 on interecho time in these iron-supplemented, MagA-expressing cells was better represented by the Jensen-Chandra model compared to the Luz-Meiboom model, whereas the Luz-Meiboom model performed better for the remaining cell types. Our findings provide an estimate of the distance scale of microscopic magnetic field variations in MagA-expressing cells, which is thought to be related to the size of iron-containing vesicles.
     
14. 

    EphA2 as a Diagnostic Imaging Target in Glioblastoma: A Positron Emission Tomography/Magnetic Resonance Imaging Study

    Simon Puttick, Brett W. Stringer, Bryan W. Day, Zara C. Bruce, Kathleen S. Ensbey, Karine Mardon, Gary J. Cowin, Kristofer J. Thurecht, Andrew K. Whittaker,Michael Fay, Andrew W. Boyd, Stephen Rose
    Molecular Imaging, vol. 14, 6, First Published July 1, 2015.
    Abstract

    Hide Preview

    Abstract

    Noninvasive imaging is a critical technology for diagnosis, classification, and subsequent treatment planning for patients with glioblastoma. It has been shown that the EphA2 receptor tyrosine kinase (RTK) is overexpressed in a number of tumors, including glioblastoma. Expression levels of Eph RTKs have been linked to tumor progression, metastatic spread, and poor patient prognosis. As EphA2 is expressed at low levels in normal neural tissues, this protein represents an attractive imaging target for delineation of tumor infiltration, providing an improved platform for image-guided therapy. In this study, EphA2-4B3, a monoclonal antibody specific to human EphA2, was labeled with ⁶⁴Cu through conjugation to the chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The resulting complex was used as a positron emission tomography (PET) tracer for the acquisition of high-resolution longitudinal PET/magnetic resonance images. EphA2-4B3-NOTA-⁶⁴Cu images were qualitatively and quantitatively compared to the current clinical standards of [¹⁸F]FDOPA and gadolinium (Gd) contrast–enhanced MRI. We show that EphA2-4B3-NOTA-⁶⁴Cu effectively delineates tumor boundaries in three different mouse models of glioblastoma. Tumor to brain contrast is significantly higher in EphA2-4B3-NOTA-⁶⁴Cu images than in [¹⁸F]FDOPA images and Gd contrast–enhanced MRI. Furthermore, we show that nonspecific uptake in the liver and spleen can be effectively blocked by a dose of nonspecific (isotype control) IgG.
     
15. 

    Monoclonal Antibody–Conjugated Superparamagnetic Iron Oxide Nanoparticles for Imaging of Epidermal Growth Factor Receptor–Targeted Cells and Gliomas

    Ketao Mu, Shun Zhang, Tao Ai, Jingjing Jiang, Yihao Yao, Lingyu Jiang, Qing Zhou, Hongbing Xiang, Yanhong Zhu, Xiangliang Yang, Wenzhen Zhu
    Molecular Imaging, vol. 14, 5, First Published May 1, 2015.
    Abstract

    Hide Preview

    Abstract

    The objective of this study was to successfully synthesize epidermal growth factor receptor monoclonal antibody–conjugated superparamagnetic iron oxide nanoparticles (EGFRmAb-SPIONs) and explore their biocompatibility and potential applications as a targeted magnetic resonance imaging (MRI) contrast agent for the EGFR-specific detection of brain glioma in vivo. After conjugation of EGFRmAb with SPIONs, the magnetic characteristics of EGFRmAb-SPIONs were investigated. Thereafter, the targeting abilities of EGFRmAb-SPIONs with MRI were qualitatively and quantitatively assessed in EGFR-positive C6 glioma cells in vitro and in a Wistar rat model bearing C6 glioma in vivo. Furthermore, the preliminary biocompatibility and toxicity of EGFRmAb-SPIONs were evaluated in normal rats through hematology assays and histopathologic analyses. Statistical analysis was performed using one-way analysis of variance and Student t-test, with a significance level of p < .05. From the results of EGFRmAb-SPION characterizations, the average particle size was 10.21 nm and the hydrodynamic diameter was 161.5 ± 2.12 nm. The saturation magnetization was 55 emu/g·Fe, and T₂ relaxivity was 92.73 s⁻¹mM⁻¹ in distilled water. The preferential accumulation of the EGFRmAb-SPIONs within glioma and subsequent MRI contrast enhancement were demonstrated both in vitro in C6 cells and in vivo in rats bearing C6 glioma. After intravenous administration of EGFRmAb-SPIONs, T₂-weighted MRI of the rat model with brain glioma exhibited an apparent hypointense region within glioma from 2 to 48 hours. The maximal image contrast was reached at 24 hours, where the signal intensity decreased and the R₂ value increased by 30% compared to baseline. However, T₂-weighted imaging of the rat model administered with SPIONs showed no visible signal changes within the tumor over the same time period. Moreover, no evident toxicities in vitro and in vivo with EGFRmAb-SPIONs were clearly identified based on the laboratory examinations. EGFRmAb-SPIONs could potentially be employed as a targeted contrast agent in the molecule-specific diagnosis of brain glioma in MRI.
     
16. 

    Gadospin F—Enhanced Magnetic Resonance Imaging for Diagnosis and Monitoring of Atherosclerosis: Validation with Transmission Electron Microscopy and X-Ray Fluorescence Imaging in the Apolipoprotein E—Deficient Mouse

    Caroline Jung, Tanja Dučić, Rudolph Reimer, Eva Koziolek, Fabian Kording, Markus Heine, Gerhard Adam, Harald Ittrich, Michael G. Kaul
    Molecular Imaging, vol. 14, 1, First Published January 1, 2015.
    Abstract

    Hide Preview

    Abstract

    The aim of this study was to investigate the feasibility of noninvasive monitoring of plaque burden in apolipoprotein E–deficient (ApoE^−/−) mice by Gadospin F (GDF)-enhanced magnetic resonance imaging (MRI). Gadolinium uptake in plaques was controlled using transmission electron microscopy (TEM) and x-ray fluorescence (XRF) microscopy. To monitor the progression of atherosclerosis, ApoE^−/− (n = 5) and wild-type (n = 2) mice were fed a Western diet and imaged at 5, 10, 15, and 20 weeks. Contrast-enhanced MRI was performed at 7 T Clinscan (Bruker, Ettlingen, Germany) before and 2 hours after intravenous injection of GDF (100 μmol/kg) to determine the blood clearance. Plaque size and contrast to noise ratio (CNR) were calculated for each time point using region of interest measurements to evaluate plaque progression. Following MRI, aortas were excised and GDF uptake was cross-validated by TEM and XRF microscopy. The best signal enhancement in aortic plaque was achieved 2 hours after application of GDF. No signal differences between pre- and postcontrast MRI were detectable in wild-type mice. We observed a gradual and considerable increase in plaque CNR and size for the different disease stages. TEM and XRF microscopy confirmed the localization of GDF within the plaque. GDF-enhanced MRI allows noninvasive and reliable estimation of plaque burden and monitoring of atherosclerotic progression in vivo.
     
17. 

    Magnetic Resonance Tracking of Endothelial Progenitor Cells Labeled with Alkyl-Polyethylenimine 2 kDa/Superparamagnetic Iron Oxide in a Mouse Lung Carcinoma Xenograft Model

    Cong Chen*, Hong Yu*, Rui Xia, Lei Wang, Hua Ai, Shiyuan Liu, Zhiming Xu, Xiangsheng Xiao, Fabao Gao
    Molecular Imaging, vol. 13, 9, First Published November 1, 2014.
    Abstract

    Hide Preview

    Abstract

    The potential of using endothelial progenitor cells (EPCs) in novel anticancer therapy and the repair of vascular injury has been increasingly recognized. In the present study, EPCs were labeled with N-alkyl-polyethylenimine 2 kDa (PEI2k)-stabilized superparamagnetic iron oxide (SPIO) to facilitate magnetic resonance imaging (MRI) of EPCs in a mouse lung carcinoma xenograft model. EPCs derived from human peripheral blood were labeled with alkyl-PEI2k/SPIO. The viability and activity of labeled cells were evaluated using proliferation, migration, and tubulogenesis assays. Alkyl-PEI2k/SPIO-labeled EPCs were injected intravenously (group 1) or mixed and injected together with A549 cells subcutaneously (group 2) into groups of six mice with severe combined immunodeficiency. The labeling efficiency with alkyl-PEI2k/SPIO at 7 mg Fe/mL concentration was approximately 100%. Quantitative analysis of cellular iron was 6.062 ± 0.050 pg/cell. No significant effects on EPC proliferation, migration, or tubulogenesis were seen after labeling. Seventesla micro-MRI showed the presence of schistic or linear hypointense regions at the tumor margins starting from days 7 to 8 after EPC administration. This gradually extended into the inner tumor layers in group 1. In group 2, tumor growth was accompanied by dispersion of low-signal intensity regions inside the tumor. Iron-positive cells identified by Prussian blue dye were seen at the sites identified using MRI. Human CD31-positive cells and mouse CD31-positive cells were present in both groups. Labeling EPCs with alkyl-PEI2k/SPIO allows noninvasive magnetic resonance investigation of EPC involvement in tumor neovasculature and is associated with excellent biocompatibility and MRI sensitivity.
     
18. 

    Ultrashort Echo Time Magnetic Resonance Imaging of the Lung Using a High-Relaxivity T₁ Blood-Pool Contrast Agent

    Joris Tchouala Nofiele, Weiran Cheng, Inga E. Haedicke, Tameshwar Ganesh, Xiao-an Zhang, Hai-Ling Margaret Cheng
    Molecular Imaging, vol. 13, 8, First Published October 1, 2014.
    Abstract

    Hide Preview

    Abstract

    The lung remains one of the most challenging organs to image using magnetic resonance imaging (MRI) due to intrinsic rapid signal decay. However, unlike conventional modalities such as computed tomography, MRI does not involve radiation and can provide functional and morphologic information on a regional basis. Here we demonstrate proof of concept for a new MRI approach to achieve substantial gains in a signal to noise ratio (SNR) in the lung parenchyma: contrast-enhanced ultrashort echo time (UTE) imaging following intravenous injection of a high-relaxivity blood-pool manganese porphyrin T₁ contrast agent. The new contrast agent increased relative enhancement of the lung parenchyma by over 10-fold compared to gadolinium diethylene triamine pentaacetic acid (Gd-DTPA), and the use of UTE boosted the SNR by a factor of 4 over conventional T₁-weighted gradient echo acquisitions. The new agent also maintains steady enhancement over at least 60 minutes, thus providing a long time window for obtaining high-resolution, high-quality images and the ability to measure a number of physiologic parameters.
     
19. 

    Manganese-Enhanced Magnetic Resonance Imaging for Early Detection and Characterization of Breast Cancers

    Mosa Alhamami*, Reza Bayat Mokhtari*, Tameshwar Ganesh*, Joris Tchouala Nofiele*, Herman Yeger, Hai-Ling Margaret Cheng
    Molecular Imaging, vol. 13, 7, First Published September 1, 2014.
    Abstract

    Hide Preview

    Abstract

    Very early cancer detection is the key to improving cure. Our objective was to investigate manganese (Mn)-enhanced magnetic resonance imaging (MRI) for very early detection and characterization of breast cancers. Eighteen NOD scid gamma mice were inoculated with MCF7, MDA, and LM2 breast cancer cells and imaged periodically on a 3 T scanner beginning on day 6. T₁-weighted imaging and T₁ measurements were performed before and 24 hours after administering MnCl₂. At the last imaging session, Gd-DTPA was administered and tumors were excised for histology (hematoxylin-eosin and CD34 staining). All mice, except for two inoculated with MCF7 cells, developed tumors. Tumors enhanced uniformly on Mn and showed clear borders. Early small tumors (# 5 mm³) demonstrated the greatest enhancement with a relative R₁ (1/T₁) change of 1.57 ± 0.13. R₁ increases correlated with tumor size (r = −.34, p − .04). Differences in R₁ increases among the three tumor subtypes were most evident in early tumors. Histology confirmed uniform cancer cell distribution within tumor masses and vasculature in the periphery, which was consistent with rim-like enhancement on Gd-DTPA. Mn-enhanced MRI is a promising approach for detecting very small breast cancers in vivo and may be valuable for very early cancer detection.
     
20. 

    Magnetic Resonance Imaging Visualization of Vulnerable Atherosclerotic Plaques at the Brachiocephalic Artery of Apolipoprotein E Knockout Mice by the Blood-Pool Contrast Agent B22956/1

    Cinzia Parolini, Marco Busnelli, Giulia S. Ganzetti, Federica Dellera, Stefano Manzini, Eugenio Scanziani, Jason L. Johnson, Cesare R. Sirtori, Giulia Chiesa
    Molecular Imaging, vol. 13, 5, First Published July 1, 2014.
    Abstract

    Hide Preview

    Abstract

    The aim of this study was to identify, by magnetic resonance imaging (MRI), the ability of the blood-pool contrast agent B22956/1 to detect atherosclerotic plaques developing at the brachiocephalic artery of apolipoprotein E knockout (apoE-KO) mice and to possibly identify vulnerable atherosclerotic lesions. After high-fat feeding for 8 or 12 weeks, MRIs of brachiocephalic arteries were acquired before and after B22956/1 administration; then vessels were removed and analyzed by histology. B22956/1 injection caused a rapid increase in plaque signal enhancement and plaque to muscle contrast values, which remained stable up to 70 minutes. A linear correlation between signal enhancement and macrophage content was found 10 minutes after B22956/1 injection (p < .01). Signal enhancement and plaque to muscle contrast values correlated with macrophage content 40 minutes after contrast agent administration (p < .01). Finally, 70 minutes after B22956/1 infusion, plaque to muscle contrast significantly correlated with the percentage of stenosis (p < .005). B22956/1 administration to high fat-fed apoE-KO mice resulted in a rapid enhancement of atherosclerotic plaques and in a great ability to rapidly visualize vulnerable plaques, characterized by a high macrophage content. These results suggest that B22956/1 could represent an interesting tool for the identification of atherosclerotic plaques potentially leading to acute cardiovascular events.
     
21. 

    Noninvasive Manganese-Enhanced Magnetic Resonance Imaging for Early Detection of Breast Cancer Metastatic Potential

    Joris Tchouala Nofiele, Gregory J. Czarnota, Hai-Ling Margaret Cheng
    Molecular Imaging, vol. 13, 1, First Published January 1, 2014.
    Abstract

    Hide Preview

    Abstract

    Cancer cells with a high metastatic potential will more likely escape and form distant tumors. Once the cancer has spread, a cure is rarely possible. Unfortunately, metastasis often proceeds unnoticed until a secondary tumor has formed. The culprit is that current imaging-based cancer screening and diagnosis are limited to assessing gross physical changes, not the earliest cellular changes that drive cancer progression. The purpose of this study is to develop a novel noninvasive magnetic resonance (MR) cellular imaging capability for characterizing the metastatic potential of breast cancer and enable early cancer detection. This MR method relies on imaging cell uptake of manganese, an endogenous calcium analogue and an MR contrast agent, to detect aggressive cancer cells. Studies on normal breast epithelial cells and three breast cancer cell lines, from nonmetastatic to highly metastatic, demonstrated that aggressive cancer cells appeared significantly brighter on MR as a result of altered cell uptake of manganese. In vivo results in nude rats showed that aggressive tumors that are otherwise unseen on conventional gadolinium-enhanced MR imaging are detected after manganese injection. This cellular MR imaging technology brings a critically needed, unique dimension to cancer imaging by enabling us to identify and characterize metastatic cancer cells at their earliest appearance.