A paradigm shift in point-of-care imaging in low-income and middle-income countries.

The concept of primary healthcare is now regarded as crucial for enhancing access to healthcare services in low-income and middle-income countries (LMICs). Technological advancements that have made many medical imaging devices smaller, lighter, portable and more affordable, and infrastructure advancements in power supply, Internet connectivity, and artificial intelligence, are all increasing the feasibility of POCI (point-of care imaging) in LMICs. Although providing imaging services at the same time as the clinic visit represents a paradigm shift in the way imaging care is typically provided in high-income countries where patients are typically directed to dedicated imaging centres, a POCI model is often the only way to provide timely access to imaging care for many patients in LIMCs. To address the growing burden of non-communicable diseases such as cancer and heart disease, bringing advanced imaging tools to the POCI will be necessary. Strategies tailored to the countries' specific needs, including training, safety and quality, will be of the utmost importance.

Education and training in radiation protection in Europe: results from the EURAMED Rocc-n-Roll project survey.

PURPOSE: To analyse the existing radiation protection (RP) education and training (E&T) capabilities in the European Union and identify associated needs, problems and challenges. METHOD: An online survey was disseminated via the EURAMED Rocc-n-Roll consortium network and prominent medical societies in the field of radiological research. The survey sections analyse the RP E&T during undergraduate, residency/internship and continuous professional development; RP E&T problems and legal implementation. Differences were analysed by European geographic regions, profession, years of professional experience and main area of practice/research. RESULTS: The majority of the 550 respondents indicated that RP topics are part of undergraduate curricula in all courses for their profession and country (55%); however, hands-on practical training is not included according to 30% of the respondents. The lack of E&T, practical aspects in current E&T, and mandatory continuing E&T were considered the major problems. The legal requirement that obtained higher implementation score was the inclusion of the practical aspects of medical radiological procedures on education (86%), and lower score was obtained for the inclusion of RP E&T on medical and dental school curriculums (61%). CONCLUSIONS: A heterogeneity in RP E&T during undergraduate, residency/internship and continuous professional development is evident across Europe. Differences were noted per area of practice/research, profession, and European geographic region. A large variation in RP E&T problem rating was also obtained.

A Multimedia Strategy to Integrate Introductory Broad-Based Radiation Science Education in US Medical Schools.

US physicians in multiple specialties who order or conduct radiological procedures lack formal radiation science education and thus sometimes order procedures of limited benefit or fail to order what is necessary. To this end, a multidisciplinary expert group proposed an introductory broad-based radiation science educational program for US medical schools. Suggested preclinical elements of the curriculum include foundational education on ionizing and nonionizing radiation (eg, definitions, dose metrics, and risk measures) and short- and long-term radiation-related health effects as well as introduction to radiology, radiation therapy, and radiation protection concepts. Recommended clinical elements of the curriculum would impart knowledge and practical experience in radiology, fluoroscopically guided procedures, nuclear medicine, radiation oncology, and identification of patient subgroups requiring special considerations when selecting specific ionizing or nonionizing diagnostic or therapeutic radiation procedures. Critical components of the clinical program would also include educational material and direct experience with patient-centered communication on benefits of, risks of, and shared decision making about ionizing and nonionizing radiation procedures and on health effects and safety requirements for environmental and occupational exposure to ionizing and nonionizing radiation. Overarching is the introduction to evidence-based guidelines for procedures that maximize clinical benefit while limiting unnecessary risk. The content would be further developed, directed, and integrated within the curriculum by local faculties and would address multiple standard elements of the Liaison Committee on Medical Education and Core Entrustable Professional Activities for Entering Residency of the Association of American Medical Colleges.

Education and training in radiation protection in Europe: an analysis from the EURAMED rocc-n-roll project.

BACKGROUND: A Strengths, weaknesses, opportunities and threats analysis was performed to understand the status quo of education and training in radiation protection (RP) and to develop a coordinated European approach to RP training needs based on stakeholder consensus and existing activities in the field. Fourteen team members represented six European professional societies, one European voluntary organisation, two international healthcare organisations and five professions, namely: Medical Physicists; Nuclear Medicine Physicians; Radiologists; Radiation Oncologists and Radiographers. Four subgroups analysed the "Strengths", "Weaknesses", "Opportunities" and "Threats" related to E&T in RP developed under previous European Union (EU) programmes and on the Guidelines on Radiation Protection Education and Training of Medical Professionals in the EU. RESULTS: Consensus agreement identified four themes for strengths and opportunities, namely: (1) existing structures and training recommendations; (2) RP training needs assessment and education & training (E&T) model(s) development; (3) E&T dissemination, harmonisation, and accreditation; (4) financial supports. Weaknesses and Threats analysis identified two themes: (1) awareness and prioritisation at a national/global level and (2) awareness and prioritisation by healthcare professional groups and researchers. CONCLUSIONS: A lack of effective implementation of RP principles in daily practice was identified. EuRnR strategic planning needs to consider processes at European, national and local levels. Success is dependent upon efficient governance structures and expert leadership. Financial support is required to allow the stakeholder professional agencies to have sufficient resources to achieve a pan European radiation protection training network which is sustainable and accredited across multiple national domains.

Subclinical Left Ventricular Dysfunction Detected by Speckle-Tracking Echocardiography in Breast Cancer Patients Treated With Radiation Therapy: A Six-Month Follow-Up Analysis (MEDIRAD EARLY-HEART study).

Background: In the case of breast cancer (BC), radiotherapy (RT) helps reduce locoregional recurrence and BC-related deaths but can lead to cardiotoxicity, resulting in an increased risk of long-term major cardiovascular events. It is therefore of primary importance to early detect subclinical left ventricular (LV) dysfunction in BC patients after RT and to determine the dose-response relationships between cardiac doses and these events. Methods: Within the frame of the MEDIRAD European project (2017-2022), the prospective multicenter EARLY-HEART study (ClinicalTrials.gov Identifier: NCT03297346) included chemotherapy naïve BC women aged 40-75 years and treated with lumpectomy and adjuvant RT. Myocardial strain analysis was provided using speckle-tracking echocardiography performed at baseline and 6 months following RT. A global longitudinal strain (GLS) reduction >15% between baseline and follow-up was defined as a GLS-based subclinical LV dysfunction. Individual patient dose distributions were obtained using multi-atlas-based auto-segmentation of the heart. Dose-volume parameters were studied for the whole heart (WH) and left ventricle (LV). Results: The sample included 186 BC women (57.5 ± 7.9 years, 64% left-sided BC). GLS-based subclinical LV dysfunction was observed in 22 patients (14.4%). These patients had significantly higher cardiac exposure regarding WH and LV doses compared to patients without LV dysfunction (for mean WH dose: 2.66 ± 1.75 Gy versus 1.64 ± 0.96 Gy, p = 0.01). A significantly increased risk of subclinical LV dysfunction was observed with the increase in the dose received to the WH [ORs from 1.13 (V5) to 1.74 (Dmean); p <0.01] and to the LV [ORs from 1.10 (V5) to 1.46 (Dmean); p <0.01]. Based on ROC analysis, the LV-V5 parameter may be the best predictor of the short-term onset of subclinical LV dysfunction. Conclusion: These results highlighted that all cardiac doses were strongly associated with the occurrence of subclinical LV dysfunction arising 6 months after BC RT. Whether measurements of GLS at baseline and 6 months after RT combined with cardiac doses can early predict efficiently subclinical events occurring 24 months after RT remains to be investigated.

Radiation dose and diagnostic reference levels for four interventional radiology procedures: results of the prospective European multicenter survey EUCLID.

OBJECTIVES: To assess information reflecting radiation dose and define diagnostic reference levels (DRL) on a European basis for four interventional radiology (IR) procedures considering clinical indication, anatomical region, and procedure. METHODS: A prospective European study was performed to provide data on the IR procedures percutaneous recanalization of iliac arteries, percutaneous recanalization of femoropopliteal arteries, transarterial chemoembolization of hepatocellular carcinoma, and percutaneous transhepatic biliary drainage. Hospitals were asked to complete a questionnaire giving information on procedure, equipment, and protocol. Patient size and weight, experience of the operator graded in number of procedures performed, and complexity level of each procedure were reported. Sixteen hospitals from 13 countries could be surveyed. The percentiles of the kerma-area product, fluoroscopy time, cumulative air kerma at the interventional reference point, and number of images were determined. The impact of equipment, year of installation, and complexity level of the procedure on dose were analyzed. RESULTS: DRLs based on clinical indication were defined. Dose values varied considerably within hospitals, between them, and within each subgroup of complexity level. The use of state-of-the-art equipment reduced dose significantly by 52%. Although dose also varied within each subgroup of complexity level, for transarterial chemoembolization of hepatocellular carcinoma and percutaneous transhepatic biliary drainage, dose significantly correlated with complexity. CONCLUSIONS: This was the first study reporting exposure practice and defining DRLs based on clinical indication for four IR procedures on a European basis. These DRLs can serve as a baseline for comparison with local practice, the study as a guideline for future surveys. KEY POINTS: • The use of state-of-the-art angiographic equipment reduces dose significantly. • A significant correlation between radiation dose and complexity level is found. • Dose values vary considerably, both within and between individual hospitals, and within each complexity level of interventional radiology procedure.

Medical imaging and nuclear medicine: a Lancet Oncology Commission.

The diagnosis and treatment of patients with cancer requires access to imaging to ensure accurate management decisions and optimal outcomes. Our global assessment of imaging and nuclear medicine resources identified substantial shortages in equipment and workforce, particularly in low-income and middle-income countries (LMICs). A microsimulation model of 11 cancers showed that the scale-up of imaging would avert 3·2% (2·46 million) of all 76·0 million deaths caused by the modelled cancers worldwide between 2020 and 2030, saving 54·92 million life-years. A comprehensive scale-up of imaging, treatment, and care quality would avert 9·55 million (12·5%) of all cancer deaths caused by the modelled cancers worldwide, saving 232·30 million life-years. Scale-up of imaging would cost US$6·84 billion in 2020-30 but yield lifetime productivity gains of $1·23 trillion worldwide, a net return of $179·19 per $1 invested. Combining the scale-up of imaging, treatment, and quality of care would provide a net benefit of $2·66 trillion and a net return of $12·43 per $1 invested. With the use of a conservative approach regarding human capital, the scale-up of imaging alone would provide a net benefit of $209·46 billion and net return of $31·61 per $1 invested. With comprehensive scale-up, the worldwide net benefit using the human capital approach is $340·42 billion and the return per dollar invested is $2·46. These improved health and economic outcomes hold true across all geographical regions. We propose actions and investments that would enhance access to imaging equipment, workforce capacity, digital technology, radiopharmaceuticals, and research and training programmes in LMICs, to produce massive health and economic benefits and reduce the burden of cancer globally.

Cumulative effective dose from recurrent CT examinations in Europe: proposal for clinical guidance based on an ESR EuroSafe Imaging survey.

In recent years, the issue of cumulative effective dose received from recurrent computed tomography examinations has become a subject of increasing concern internationally. Evidence, predominantly from the USA, has shown that a significant number of patients receive a cumulative effective dose of 100 mSv or greater. To obtain a European perspective, EuroSafe Imaging carried out a survey to collect European data on cumulative radiation exposure of patients from recurrent computed tomography examinations. The survey found that a relatively low percentage of patients (0.5%) received a cumulative effective dose equal to or higher than 100 mSv from computed tomography, most of them having an oncological disease. However, there is considerable variation between institutions as these values ranged from 0 to 2.72%, highlighting that local practice or, depending on the institution and its medical focus, local patient conditions are likely to be a significant factor in the levels of cumulative effective dose received, rather than this simply being a global phenomenon. This paper also provides some practical actions to support the management of cumulative effective dose and to refine or improve practice where recurrent examinations are required. These actions are focused around increasing awareness of referring physicians through encouraging local dialogue, actions focused on optimisation where a team approach is critical, better use of modern equipment and the use of Dose Management and Clinical Decision Support Systems together with focused clinical audits. The proper use of cumulative effective dose should be part of training programmes for referrers and practitioners, including what information to give to patients. Radiation is used to the benefit of patients in diagnostic procedures such as CT examinations, and in therapeutic procedures like the external radiation treatment for cancer. However, radiation is also known to increase the risk of cancer. To oversee this risk, the cumulative effective dose (CED) received by a patient from imaging procedures over his or her life is important. In this paper, the authors, on behalf of EuroSafe Imaging, report on a survey carried out in Europe that aims to estimate the proportion of patients that undergo CT examinations and are exposed to a CED of more than 100 mSv. At the same time, the survey enquires about and underlines radiologists' measures and radiology departments' strategies to limit such exposure. Over the period of 2015-2018, respondents reported that 0.5% (0-2.72%) of patients were exposed to a CED of ≥ 100 mSv from imaging procedures. The background radiation dose in Europe depends on the location, but it is around 2.5 mSv per year. It is obvious that patients with cancer, chronic diseases and trauma run the highest risk of having a high CED. However, even if the number of patients exposed to ≥ 100 mSv is relatively low, it is important to lower this number even further. Measures could consist in using procedures that do not necessitate radiation, using very low dose procedures, being very critical in requiring imaging procedures and increasing awareness about the issue. KEY POINTS: • A relatively low percentage of patients (0.5%) received a cumulative effective dose from CT computed tomography equal to or greater than 100 mSv, in Europe, most of them having an oncological disease. • There is a wide range in the number of patients who receive cumulative effective dose equal to or greater than 100 mSv (0-2.72%) and optimisation should be improved. • Increasing the awareness of referring physicians through encouraging local dialogue, concrete actions focused on optimisation and development of dose management systems is suggested.

CT diagnostic reference levels based on clinical indications: results of a large-scale European survey.

OBJECTIVES: The objective of this study was to investigate the feasibility of defining diagnostic reference levels (DRLs) on a European basis for specific clinical indications (CIs), within the context of the European Clinical DRLs (EUCLID) European Commission project. METHODS: A prospective, multicenter, industry-independent European study was performed to provide data on 10 CIs (stroke, chronic sinusitis, cervical spine trauma, pulmonary embolism, coronary calcium scoring, coronary angiography, lung cancer, hepatocellular carcinoma, colic/abdominal pain, and appendicitis) via an online survey that included information on patient clinical, technical, and dosimetric parameters. Data from at least 20 patients per CI were requested from each hospital. To establish DRLs, a methodology in line with the International Commission on Radiological Protection (ICRP) Report 135 good practice recommendations was followed. RESULTS: Data were collected from 19 hospitals in 14 European countries on 4299 adult patients and 10 CIs to determine DRLs. DRLs differ considerably between sites for the same CI. Differences were attributed mainly to technical protocol and variable number of phases/scan lengths. Stroke and hepatocellular carcinoma were the CIs with the highest DRLs. Coronary calcium scoring had the lowest DRL value. Comparison with published literature was limited, as there was scarce information on DRLs based on CI. CONCLUSIONS: This is the first study reporting on feasibility of establishing CT DRLs based on CI using European data. Resulting values will serve as a baseline for comparison with local radiological practice, national authorities when DRLs are set/updated, or as a guideline for local DRL establishment. KEY POINTS: • First study reporting on the feasibility of establishing CT diagnostic reference levels based on clinical indication using data collected across Europe. • Only one-fourth of the hospitals had CT machines less than 5 years old. • Large dose variations were observed among hospitals and CT protocols were quite different between hospitals.

ESR EuroSafe Imaging and its role in promoting radiation protection - 6 years of success.

This article introduces the European Society of Radiology's EuroSafe Imaging initiative in the year of its 6th anniversary. The European and global radiation protection frameworks are outlined and the role of the EuroSafe Imaging initiative's Call for Action in successfully achieving international radiation protection goals as set out by those frameworks is detailed.

Improving justification of medical exposures using ionising radiation: considerations and approaches from the European Society of Radiology.

This discussion paper has been produced within the context of the European Society of Radiology EuroSafe Imaging initiative and considers primarily the issues and challenges associated with justification of medical exposures using ionising radiation for individual patient diagnostic imaging procedures. It addresses both regulatory requirements and practical considerations and discusses approaches that are intended to improve justification.

Radiation dose management systems-requirements and recommendations for users from the ESR EuroSafe Imaging initiative.

The European Directive 2013/59/Euratom requires member states of the European Union to ensure justification and optimisation of radiological procedures and store information on patient exposure for analysis and quality assurance. The EuroSafe Imaging campaign of the European Society of Radiology created a working group (WG) on "Dose Management" with the aim to provide European recommendations on the implementation of dose management systems (DMS) in clinical practice. The WG follows Action 4: "Promote dose management systems to establish local, national, and European diagnostic reference levels (DRL)" of the EuroSafe Imaging Call for Action 2018. DMS are designed for medical practitioners, radiographers, medical physics experts (MPE) and other health professionals involved in imaging to support their tasks and duties of radiation protection in accordance with local and national requirements. The WG analysed requirements and critical points when installing a DMS and classified the individual functions at different performance levels. KEY POINTS: • DMS are very helpful software tools for monitoring patient exposure, optimisation, compliance with DRLs and quality assurance. • DMS can help to fulfil dosimetric aspects of the European Directive 2013/59/Euratom. • The EuroSafe WG analyses DMS requirements and gives recommendations for users.

Metastatic renal carcinoma: evaluation of antiangiogenic therapy with dynamic contrast-enhanced CT.

PURPOSE: To determine whether tumor perfusion parameters assessed by using dynamic contrast material-enhanced computed tomography (CT) could help predict and detect response in patients receiving antiangiogenic therapy for metastatic renal cell carcinoma. MATERIALS AND METHODS: Institutional ethics committee approval and informed consent were obtained. In two phase-III trials involving 51 patients with metastatic renal cell carcinoma (38 men, 13 women; age range, 30-80 years) receiving antiangiogenic drugs (sorafenib [n = 10], sunitinib [n = 22]), a placebo (n = 12), or interferon alfa (n = 7), serial dynamic contrast-enhanced CT was performed, during 90 seconds before and after injection of 80 mL of iobitridol. Perfusion parameters of a target metastatic tumor (tumor blood flow [TBF], tumor blood volume [TBV], mean transit time, and vascular permeability-surface area product) were calculated. Values before and after treatment were compared by using a Wilcoxon signed rank test, and relative changes in groups were compared by using the Wilcoxon rank sum test. Results were compared with Response Evaluation Criteria in Solid Tumors response and with progression-free and overall survival by using Kaplan-Meier curves. RESULTS: Among patients receiving antiangiogenic drugs, baseline perfusion parameters were higher in responders than in stable patients (TBF = 245.3 vs 119.5 mL/min/100 mL, P = .04; TBV = 15.5 vs 8.2 mL/100 mL, P = .02) but were not significantly predictive of survival. After the first cycle of treatment, there was a significant decrease in TBF (162.5 vs 76.7 mL/min/100 mL, P = .0002) and TBV (9.1 vs 3.9 mL/100 mL, P < .0001) in patients receiving antiangiogenic treatment. CONCLUSION: Renal carcinoma perfusion parameters determined with dynamic contrast-enhanced CT can help predict biologic response to antiangiogenic drugs before beginning therapy and help detect an effect after a single cycle of treatment.

Baseline results of the Depiscan study: a French randomized pilot trial of lung cancer screening comparing low dose CT scan (LDCT) and chest X-ray (CXR).

BACKGROUND: Lung cancer has the highest mortality-rate per cancer, with an overall 5-year survival <15%. Several non-randomized studies pointed out the high sensitivity of low dose computed tomography (LDCT) to detect early stage lung cancer. In France, Depiscan, a pilot RCT of LDCT versus chest X-ray (CXR), started on October 2002 to determine the feasibility of enrollment by general practitioners (GPs), investigations and diagnostic procedures by university hospital radiologists and multidisciplinary teams, data management by centralized clinical research assistants, and anticipate the future management of a large national trial. METHODS: GPs and occupational physicians (OPs) selected and enrolled 1000 subjects in 1 year. Eligible subjects were asymptomatic males or females aged 50-75 years with a current or former cigarette smoking history of >/=15 cigarettes per day for at least 20 years (former smokers having quit <15 years prior to enrollment). Based to randomization, annual LDCT or CXR screenings were planned at baseline and annually for 2 years. RESULTS: Between October 2002 and December 2004, 765 subjects were enrolled by 89 out of the 232 participating GPs and OPs. Complete clinical and imaging baseline data were available for 621 individuals out of the 765 enrolled, due to 144 noncompliant subjects who withdrew their consent. At least one nodule was detected in 152 out of 336 subjects (45.2%) in the LDCT screening, versus 21 out of 285 subjects (7.4%) in the CXR screening arm. Eight lung cancers were detected in the LDCT arm and one in the CXR arm. DISCUSSION: This pilot trial allows estimating that non-calcified nodules are 10 [6.36-17.07] times more often detected from LDCT than from CXR. However enrollment by GPs was more difficult than expected with 41% active investigators and a high rate (19%) of noncompliant patients. This experience speaks to the need for a high level of GPs formation and a large, coordinated clinical research team in such a trial. TRIAL REGISTRATION NUMBER: 02526.

Software volumetric evaluation of doubling times for differentiating benign versus malignant pulmonary nodules.

OBJECTIVE: The purpose of our study was to evaluate the reliability of software-calculated doubling times for discerning malignant versus benign nodules. MATERIALS AND METHODS: CT lung analysis volumetric software was used to retrospectively calculate the doubling times of 63 solid noncalcified nodules by comparing nodule volumes on baseline and follow-up CT scans obtained a median of 3.7 months apart. A final diagnosis based on validated criteria was available for all 63 nodules. All CT examinations were performed with 1.25-mm-thick slices on a four-detector unit. Taking 500 days as the upper value for malignancies, we evaluated whether the software-calculated doubling times could be used to distinguish malignant from benign solid nodules. We also examined whether the relative volume variation of benign nodules correlated with initial nodule size, interscan interval, or differences in contrast administration or exposure parameters between baseline and follow-up CT. RESULTS: There were 52 benign and 11 malignant nodules. Benign nodules had a median doubling time of 947 days and a mean relative volume variation of -4.4% (range, -50% to 38%). Malignant nodules had a median doubling time of 117 days and a mean relative volume variation of 102% (22-462%). The sensitivity, specificity, and negative and positive predictive values of the volumetric software for diagnosing malignancy were 91% (95% confidence interval [CI], 0.59-1.00), 90% (95% CI, 0.79-0.97), 98% (95% CI, 0.89-1.00), and 67% (95% CI, 0.38-0.88), respectively. No correlation was found between the relative volume variation of benign nodules and their initial size, the interscan interval, or differences in contrast administration or exposure parameters between the two CT examinations. CONCLUSION: Software-calculated pulmonary nodule doubling times of more than 500 days have a 98% negative predictive value for the diagnosis of solid malignant pulmonary nodules. This method may be useful for diagnosing malignant pulmonary nodules on follow-up CT.

Early modifications of hepatic perfusion measured by functional CT in a rat model of hepatocellular carcinoma using a blood pool contrast agent.

Macromolecular contrast-enhanced functional CT was performed to characterize early perfusion changes in hepatocellular carcinoma (HCC). Fourteen rats with chemically induced primary liver tumors ranging pathologically from hyperplasia to HCC and 15 control rats were investigated. Two dynamic CT scans using an experimental macromolecular contrast agent were performed on a single slice 11 and 18 weeks after tumor induction followed by pathological examination. A deconvolution mathematical model was applied, yielding the hepatic perfusion index (HPI), mean transit time (MTT), liver distribution volume (LDV) and arterial, portal and total blood flows (FA, FP, FT). Analysis was performed on one slice per rat, containing overall two hyperplasia, six dysplasia and 15 HCC. On the first scans, HCC at an early pathological stage had a low FP (-30%, P=0.002) but a normal arterial-portal balance. On the scan contemporary to pathology, HCC perfusion parameters showed an inversion of the arterial-portal balance (HPI +212%, P<0.0001), with a high FA (+56%, P=0.002) and a low FP (-69%, P<0.0001). Sensitivity and specificity of detection of HCC by perfusion CT were high (87 and 80%) on late scans; but also on the earlier scans (86 and 65%), even though only one (7%) was visible to the eye. Perfusion-CT allowed early detection of HCC. This technique could contribute in the detection and characterization of liver lesions in clinical studies.

Pulmonary nodules: preliminary experience with three-dimensional evaluation.

PURPOSE: To evaluate software designed to calculate pulmonary nodule volume in three dimensions. MATERIALS AND METHODS: Fifty-four solid noncalcified pulmonary nodules measuring 5-18 mm in diameter were studied with computed tomographic (CT) volumetric software. Baseline CT examinations were performed for various indications by using four-detector row multisection CT units, 1.25- or 2.50-mm sections, and a standard reconstruction algorithm. The percentage of successful nodule segmentations, as well as intraobserver variability, interreader agreement, and global repeatability of calculated volumes, was determined on the basis of consecutive measurements performed three times by three different radiologists by using the Bland and Altman method. The software was used to calculate the doubling time of 22 nodules for which a final diagnosis and comparable CT scans were available. RESULTS: Fifty-two (96%) of the 54 nodules were successfully segmented, allowing their volume to be calculated. Repeatability was high: There was no variation in the nine measurements of 35 (67%) of the 52 nodules. The coefficient of variation for the remaining 17 nodules (33%) was 2.26%. Bland and Altman 95% limits of acceptability, calculated on the basis of log-transformed data, yielded a maximum software measurement error of 6.38% of the previous volume measurement. Doubling time ranged from 4 to 188 years for the 13 benign nodules and from 37 to 216 days for the nine malignant nodules. CONCLUSION: Software volumetric analysis yielded repeatable estimates for 96% of the nodules examined. All software-calculated doubling times were in keeping with the benign or malignant nature of the nodules.

Glucose-receptor MR imaging of tumors: study in mice with PEGylated paramagnetic niosomes.

PURPOSE: To evaluate a magnetic resonance (MR) imaging contrast agent for tumor detection based on paramagnetic nonionic vesicles (niosomes) bearing polyethylene glycol (PEG) and glucose conjugates for the targeting of overexpressed glucose receptors. MATERIALS AND METHODS: Four gadobenate dimeglumine-loaded niosome preparations including nonconjugated niosomes, niosomes bearing glucose conjugates (N-palmitoyl glucosamine [NPG]), niosomes bearing PEG 4400, and niosomes bearing both PEG and NPG were tested. In vitro cellular uptake was measured at electron paramagnetic resonance (EPR) after incubation with human prostate carcinoma, PC3, cells. In vivo distribution was studied at MR imaging 6, 12, and 24 hours after injection, with assessment of tumor, brain, liver, and muscle signal intensity (SI) in 49 mice bearing PC3 cells. Efficiency of targeted contrast agents was assessed with tumor-to-muscle contrast-to-noise ratio (CNR). Testing for differences was performed with analysis of variance followed by a posteriori Fisher test. RESULTS: In vitro, gadolinium could be detected at EPR only in cell pellets incubated with niosomes bearing glucose conjugates or niosomes bearing both glucose conjugates and PEG (4.9. 10(-15) and 4.5. 10(-15) mol gadolinium per PC3 cell). In vivo, marked predominant tumor enhancement was demonstrated 24 hours after injection of glycosylated PEG niosomes (P <.01); no significant differences were observed following injection of nonconjugated niosomes, glycosylated niosomes, or PEG 4400 niosomes. Twenty-four hours after injection, sole presence of NPG or PEG 4400 on the surface of the niosome led to higher tumor-to-muscle CNR than that observed after injection of nonconjugated niosomes (CNR of 3.3 +/- 0.7 [SD], 3.4 +/- 2.2, and 0 +/- 1.9). Combination of NPG and PEG led to even higher tumor-to-muscle CNR (6.3 +/- 2.2). CONCLUSION: Combination of PEG and glucose conjugates on the surface of niosomes significantly improved tumor targeting of an encapsulated paramagnetic agent assessed with MR imaging in a human carcinoma xenograft model.