Modeling Gadoxetate Liver Uptake and Efflux Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging Enables Preclinical Quantification of Transporter Drug-Drug Interactions.

OBJECTIVES: The aim of this study was to model the in vivo transporter-mediated uptake and efflux of the hepatobiliary contrast agent gadoxetate in the liver. The efficacy of the proposed technique was assessed for its ability to provide quantitative insights into drug-drug interactions (DDIs), using rifampicin as inhibitor. MATERIALS AND METHODS: Three groups of C57 mice were scanned twice with a dynamic gadoxetate-enhanced magnetic resonance imaging protocol, using a 3-dimensional spoiled gradient-echo sequence for approximately 72 minutes. Before the second magnetic resonance imaging session, 2 of the groups received a rifampicin dose of 20 (n = 7) or 40 (n = 7) mg/kg, respectively. Data from regions of interest in the liver were analyzed using 2 simplifications of a 2-compartment uptake and efflux model to provide estimates for the gadoxetate uptake rate (ki) into the hepatocytes and its efflux rate (kef) into the bile. Both models were assessed for goodness-of-fit in the group without rifampicin (n = 9), and the appropriate model was selected for assessing the ability to monitor DDIs in vivo. RESULTS: Seven of 9 mice from the group without rifampicin were assessed for model implementation and reproducibility. A simple 3 parameter model (ki, kef, and extracellular space, vecs) adequately described the observed liver concentration time series with mean ki = 0.47 ± 0.11 min and mean kef = 0.039 ± 0.016 min. Visually, the area under the liver concentration time profile was reduced for the groups receiving rifampicin. Furthermore, tracer kinetic modeling demonstrated a significant dose-dependent decrease in the uptake (5.9- and 17.3-fold decrease for 20 mg/kg and 40 mg/kg, respectively) and efflux rates (2.2- and 7.9-fold decrease) compared with the first scan for each group. CONCLUSIONS: This study presents the first in vivo implementation of a 2-compartment uptake and efflux model to monitor DDIs at the transporter-protein level, using the clinically relevant organic anion transporting polypeptide inhibitor rifampicin. The technique has the potential to be a novel alternative to other methods, allowing real-time changes in transporter DDIs to be measured directly in vivo.

Effects of supplemental vibrational force on space closure, treatment duration, and occlusal outcome: A multicenter randomized clinical trial.

INTRODUCTION: A multicenter parallel 3-arm randomized clinical trial was carried out in 3 university hospitals in the United Kingdom to investigate the effect of supplemental vibratory force on space closure and treatment outcome with fixed appliances. METHODS: Eighty-one subjects less than 20 years of age with mandibular incisor irregularity undergoing extraction-based fixed appliance treatment were randomly allocated to supplementary (20 minutes/day) use of an intraoral vibrational device (AcceleDent; OrthoAccel Technologies, Houston, Tex) (n = 29), an identical nonfunctional (sham) device (n = 25), or fixed-appliance only (n = 27). Space closure in the mandibular arch was measured from dental study casts taken at the start of space closure, at the next appointment, and at completion of space closure. Final records were taken at completion of treatment. Data were analyzed blindly on a per-protocol basis with descriptive statistics, 1-way analysis of variance, and linear regression modeling with 95% confidence intervals. RESULTS: Sixty-one subjects remained in the trial at start of space closure, with all 3 groups comparable for baseline characteristics. The overall median rate of initial mandibular arch space closure (primary outcome) was 0.89 mm per month with no difference for either the AcceleDent group (difference, -0.09 mm/month; 95% CI, -0.39 to 0.22 mm/month; P = 0.57) or the sham group (difference, -0.02 mm/month; 95% CI, -0.32 to 0.29 mm/month; P = 0.91) compared with the fixed only group. Similarly, no significant differences were identified between groups for secondary outcomes, including overall treatment duration (median, 18.6 months; P >0.05), number of visits (median, 12; P >0.05), and percentage of improvement in the Peer Assessment Rating (median, 90.0%; P >0.05). CONCLUSIONS: Supplemental vibratory force during orthodontic treatment with fixed appliances does not affect space closure, treatment duration, total number of visits, or final occlusal outcome. REGISTRATION: NCT02314975. PROTOCOL: The protocol was not published before trial commencement. FUNDING: AcceleDent units were donated by OrthoAccel Technologies; no contribution to the conduct or the writing of this study was made by the manufacturer.

Evaluation of non-contrast MRI biomarkers in lupus nephritis.

OBJECTIVES: To investigate the association of novel non-contrast MRI biomarkers with standard measurements of renal function and renal disease activity in lupus. METHODS: A pilot study of lupus nephritis (LN) and lupus non-nephritis (LNN) patients, and healthy volunteers (HV), was undertaken. Multi-modal renal MRI was performed including sequences for arterial spin labelling (ASL) measuring blood flow, diffusion tensor imaging (DTI), measuring microstructural disruption, and effective transverse relaxation time (T2*) which is a biomarker of micro-haemorrhage. MRI measurements were compared with urinary protein creatinine ratio (uPCR) and estimated glomerular filtration rate (eGFR) measurements in the whole study population, then differences in imaging measurements between the groups were explored. RESULTS: 21 patients (6 LN, 8 LNN and 7 HV) completed the study, although ASL data were not available in 4 subjects. In the whole cohort, eGFR correlated significantly with the apparent diffusion coefficient measurement from DTI in the medulla (r=0.47, p=0.03). uPCR correlated strongly with the fractional anisotropy (FA) DTI measurement in the cortex and moderately with T2* measurements (rho=-0.71, p<0.001 and rho=-0.53, p=0.013, respectively). Delayed blood flow to the medulla was found in LN subjects and there was a trend towards lower FA values in the cortex, suggesting micro-structural disruption (p=0.04 and p=0.07, respectively). CONCLUSIONS: This preliminary study demonstrates that non-contrast renal MRI biomarkers are associated with standard measures of disease activity in lupus. The potential utility of these non-invasive biomarkers warrants further investigation, as there is an unmet need for reliable biomarkers of disease activity in lupus nephritis.

Quantitative Assessment of Liver Function Using Gadoxetate-Enhanced Magnetic Resonance Imaging: Monitoring Transporter-Mediated Processes in Healthy Volunteers.

OBJECTIVE: The objective of this study was to use noninvasive dynamic contrast-enhanced magnetic resonance imaging (MRI) techniques to study, in vivo, the distribution and elimination of the hepatobiliary contrast agent gadoxetate in the human body and characterize the transport mechanisms involved in its uptake into hepatocytes and subsequent efflux into the bile using a novel tracer kinetic model in a group of healthy volunteers. MATERIALS AND METHODS: Ten healthy volunteers (age range, 18-29 years), with no history of renal or hepatic impairment, were recruited via advertisement. Participants attended 2 MRI visits (at least a week apart) with gadoxetate as the contrast agent. Dynamic contrast-enhanced MRI data were acquired for approximately 50 minutes with a 3-dimensional gradient-echo sequence in the axial plane, at a temporal resolution of 6.2 seconds. Data from regions of interest drawn in the liver were analyzed using the proposed 2-compartment uptake and efflux model to provide estimates for the uptake rate of gadoxetate in hepatocytes and its efflux rate into the bile. Reproducibility statistics for the 2 visits were obtained to examine the robustness of the technique and its dependence in acquisition time. RESULTS: Eight participants attended the study twice and were included into the analysis. The resulting images provided the ability to simultaneously monitor the distribution of gadoxetate in multiple organs including the liver, spleen, and kidneys as well as its elimination through the common bile duct, accumulation in the gallbladder, and excretion in the duodenum. The mean uptake (ki) and efflux (kef) rates in hepatocytes, for the 2 visits using the 50-minute acquisition, were 0.22 ± 0.05 and 0.017 ± 0.006/min, respectively. The hepatic extraction fraction was estimated to be 0.19 ± 0.04/min. The variability between the 2 visits within the group level (95% confidence interval; ki: ±0.02/min, kef: ±0.004/min) was lower compared with the individual variability (repeatability; ki: ±0.06/min, kef: ±0.012/min). Data truncation demonstrated that the uptake rate estimates retained their precision as well as their group and individual reproducibility down to approximately 10 minutes of acquisition. Efflux rate estimates were underestimated (compared with the 50-minute acquisition) as the duration of the acquisition decreased, although these effects were more pronounced for acquisition times shorter than approximately 30 minutes. CONCLUSIONS: This is the first study that reports estimates for the hepatic uptake and efflux transport process of gadoxetate in healthy volunteers in vivo. The results highlight that dynamic contrast-enhanced MRI with gadoxetate can provide novel quantitative insights into liver function and may therefore prove useful in studies that aim to monitor liver pathology, as well as being an alternative approach for studying hepatic drug-drug interactions.

Effect of supplemental vibrational force on orthodontically induced inflammatory root resorption: A multicenter randomized clinical trial.

INTRODUCTION: A multicenter parallel 3-arm randomized clinical trial was carried out in 1 university and 2 district hospitals in the United Kingdom to investigate the effect of supplemental vibrational force on orthodontically induced inflammatory root resorption (OIIRR) during the alignment phase of fixed appliance therapy. METHODS: Eighty-one subjects less than 20 years old with mandibular incisor irregularity undergoing extraction-based fixed-appliance treatment were randomly allocated to supplementary (20 minutes a day) use of an intraoral vibrational device (AcceleDent; OrthoAccel Technologies, Houston, Tex) (n = 29), an identical nonfunctional (sham) device (n = 25), or fixed appliances only (n = 27). OIIRR was measured blindly from long-cone periapical radiographs of the maxillary right central incisor taken at the start of treatment and the end of alignment when a 0.019 × 0.025-in stainless steel archwire was placed (mean follow-up, 201.6 days; 95% confidence interval [CI], 188.6-214.6 days). Data were analyzed blindly on a per-protocol basis because losses to follow-up were minimal, with descriptive statistics, 1-way analysis of variance, and univariable and multivariable regression modeling. RESULTS: Nine patients were excluded from the analysis; they were evenly distributed across the groups. Mean overall OIIRR measured among the 72 patients was 1.08 mm (95% CI, 0.89-1.27 mm). Multivariable regression indicated no significant difference in OIIRR for the AcceleDent (difference, 0.22 mm; 95% CI, -0.14-0.72; P = 0.184) and AcceleDent sham groups (difference, 0.29 mm; 95% CI, -0.15-0.99; P = 0.147) compared with the fixed-appliance-only group, after accounting for patient sex, age, malocclusion, extraction pattern, alignment time, maximum pain experienced, history of dentoalveolar trauma, and initial root length of the maxillary right central incisor. No other side-effects were recorded apart from pain and OIIRR. CONCLUSIONS: The use of supplemental vibrational force during the alignment phase of fixed appliance orthodontic treatment does not affect OIIRR associated with the maxillary central incisor. REGISTRATION: ClinicalTrials.gov (NCT02314975). PROTOCOL: The protocol was not published before trial commencement. FUNDING: Functional and sham AcceleDent units were donated by the manufacturer; there was no contribution to the conduct or the writing of this study.

Supplemental vibrational force does not reduce pain experience during initial alignment with fixed orthodontic appliances: a multicenter randomized clinical trial.

This prospective randomized trial investigated the effect of supplemental vibrational force on orthodontic pain during alignment with fixed-appliances. Eighty-one subjects < 20 years-old undergoing extraction-based fixed-appliance treatment were randomly allocated to supplementary (20-minutes/day) use of an intra-oral vibrational device (AcceleDent(®)) (n = 29); an identical non-functional (sham) device (n = 25) or fixed-appliances only (n = 27). Each subject recorded pain intensity (using a 100-mm visual-analogue scale) and intake of oral analgesia in a questionnaire, following appliance-placement (T1) and first-adjustment (T2) for 1-week (immediately-after, 4, 24, 72-hours and at 1-week). Mean maximum-pain for the total sample was 72.96 mm [SD 21.59; 95%CI 68.19-77.74 mm] with no significant differences among groups (P = 0.282). Subjects taking analgesics reported slightly higher maximum-pain although this was not significant (P = 0.170). The effect of intervention was independent of analgesia (P = 0.883). At T1 and T2, a statistically and clinically significant increase in mean pain was seen at 4 and 24-hours, declining at 72-hours and becoming insignificant at 1-week. For mean alignment-rate, pain-intensity and use of analgesics, no significant differences existed between groups (P > 0.003). The only significant predictor for mean pain was time. Use of an AcceleDent vibrational device had no significant effect on orthodontic pain or analgesia consumption during initial alignment with fixed appliances.

An integrated characterization of serological, pathological, and functional events in doxorubicin-induced cardiotoxicity.

Many efficacious cancer treatments cause significant cardiac morbidity, yet biomarkers or functional indices of early damage, which would allow monitoring and intervention, are lacking. In this study, we have utilized a rat model of progressive doxorubicin (DOX)-induced cardiomyopathy, applying multiple approaches, including cardiac magnetic resonance imaging (MRI), to provide the most comprehensive characterization to date of the timecourse of serological, pathological, and functional events underlying this toxicity. Hannover Wistar rats were dosed with 1.25 mg/kg DOX weekly for 8 weeks followed by a 4 week off-dosing "recovery" period. Electron microscopy of the myocardium revealed subcellular degeneration and marked mitochondrial changes after a single dose. Histopathological analysis revealed progressive cardiomyocyte degeneration, hypertrophy/cytomegaly, and extensive vacuolation after two doses. Extensive replacement fibrosis (quantified by Sirius red staining) developed during the off-dosing period. Functional indices assessed by cardiac MRI (including left ventricular ejection fraction (LVEF), cardiac output, and E/A ratio) declined progressively, reaching statistical significance after two doses and culminating in "clinical" LV dysfunction by 12 weeks. Significant increases in peak myocardial contrast enhancement and serological cardiac troponin I (cTnI) emerged after eight doses, importantly preceding the LVEF decline to <50%. Troponin I levels positively correlated with delayed and peak gadolinium contrast enhancement, histopathological grading, and diastolic dysfunction. In summary, subcellular cardiomyocyte degeneration was the earliest marker, followed by progressive functional decline and histopathological manifestations. Myocardial contrast enhancement and elevations in cTnI occurred later. However, all indices predated "clinical" LV dysfunction and thus warrant further evaluation as predictive biomarkers.

Noninvasive tumor hypoxia measurement using magnetic resonance imaging in murine U87 glioma xenografts and in patients with glioblastoma.

PURPOSE: There is a clinical need for noninvasive, nonionizing imaging biomarkers of tumor hypoxia and oxygenation. We evaluated the relationship of T1 -weighted oxygen-enhanced magnetic resonance imaging (OE-MRI) measurements to histopathology measurements of tumor hypoxia in a murine glioma xenograft and demonstrated technique translation in human glioblastoma multiforme. METHODS: Preclinical evaluation was performed in a subcutaneous murine human glioma xenograft (U87MG). Animals underwent OE-MRI followed by dynamic contrast-enhanced MRI (DCE-MRI) and histological measurement including reduced pimonidazole adducts and CD31 staining. Area under the curve (AUC) was measured for the R1 curve for OE-MRI and the gadolinium concentration curve for DCE-MRI. Clinical evaluation in five patients used analogous imaging protocols and analyses. RESULTS: Changes in AUC of OE-MRI (AUCOE ) signal were regionally heterogeneous across all U87MG tumors. Tumor regions with negative AUCOE typically had low DCE-MRI perfusion, had positive correlation with hypoxic area (P = 0.029), and had negative correlation with vessel density (P = 0.004). DCE-MRI measurements did not relate to either hypoxia or vessel density in U87MG tumors. Clinical data confirmed comparable signal changes in patients with glioblastoma. CONCLUSION: These data support further investigation of T1 -weighted OE-MRI to identify regional tumor hypoxia. The quantification of AUCOE has translational potential as a clinical biomarker of hypoxia.

Assessment of gadoxetate DCE-MRI as a biomarker of hepatobiliary transporter inhibition.

Drug-induced liver injury (DILI) is a clinically important adverse drug reaction, which prevents the development of many otherwise safe and effective new drugs. Currently, there is a lack of sensitive and specific biomarkers that can be used to predict, assess and manage this toxicity. The aim of this work was to evaluate gadoxetate-enhanced MRI as a potential novel biomarker of hepatobiliary transporter inhibition in the rat. Initially, the volume fraction of extracellular space in the liver was determined using gadopentetate to enable an estimation of the gadoxetate concentration in hepatocytes. Using this information, a compartmental model was developed to characterise the pharmacokinetics of hepatic uptake and biliary excretion of gadoxetate. Subsequently, we explored the impact of an investigational hepatobiliary transporter inhibitor on the parameters of the model in vivo in rats. The investigational hepatobiliary transporter inhibitor reduced both the rate of uptake of gadoxetate into the hepatocyte, k1 , and the Michaelis-Menten constant, Vmax , characterising its excretion into bile, whereas KM values for biliary efflux were increased. These effects were dose dependent and correlated with effects on plasma chemistry markers of liver dysfunction, in particular bilirubin and bile acids. These results indicate that gadoxetate-enhanced MRI provides a novel functional biomarker of inhibition of transporter-mediated hepatic uptake and clearance in the rat. Since gadoxetate is used clinically, the technology has the potential to provide a translatable biomarker of drug-induced perturbation of hepatic transporters that may also be useful in humans to explore deleterious functional alterations caused by transporter inhibition.

Soft tissue examination of the fetal rat and rabbit head by magnetic resonance imaging.

The use of magnetic resonance imaging of the fetal rat and rabbit head, as an alternative to the traditional methods of fixation and preparation of serial sections, is described. Labeled magnetic resonance images of normal head anatomy have been provided as a reference for use when evaluating the internal structures of the head.

Warthin's tumour and facial nerve palsy: an unusual association.

We describe a man with Warthin's tumour diagnosed on core biopsy, who presented with ipsilateral facial palsy. He was managed conservatively with subsequent resolution of the palsy, which suggested many diseases. The association of a benign parotid neoplasm with facial palsy is unusual, and appropriate investigations are essential for accurate diagnosis and surgical planning.

Ultrasound guided Core Biopsy, Fine Needle Aspiration Cytology and Surgical Excision Biopsy in the diagnosis of metastatic squamous cell carcinoma in the head and neck: an eleven year experience.

INTRODUCTION: This study aims to review our 11 year experience of diagnosing metastatic squamous cell carcinoma presenting as head and neck lumps. The techniques of Ultrasound guided Core Biopsy (USCB), Fine Needle Aspiration Cytology (FNAC) and Surgical Excision Biopsy (SEB) are compared. MATERIALS AND METHODS: All patients with metastatic squamous cell carcinoma (SCC) involving the lymph nodes of the head and neck or parotid gland, diagnosed at Eastbourne District General Hospital between January 1998 and November 2009 were identified. The following data items were collated: biopsy location (e.g. cervical lymph node or parotid), any history of likely primary SCC and site, type of biopsy used to establish a conclusive diagnosis (index diagnostic technique), previous biopsies, the technique and their results, subsequent histology results. RESULTS: A total of 90 patients were diagnosed with metastatic squamous cell carcinoma. The index diagnostic technique was USCB in 48 patients, FNAC in 29 and SEB in 13. In 72 (80%) patients the index biopsy was the sole tissue sample taken prior to surgery or other treatment. The remaining 18 patients underwent a total of 22 previous biopsies prior to the index biopsy. 95% (21/22) of these previous biopsies were non-definitive FNAC and 5% (1/22) was a non-definitive USCB. FNACs also demonstrated the highest non-diagnostic rate (42%). The accuracy of USCB and FNAC in correlating with final histopathology was 97% and 85% respectively. CONCLUSIONS: USCB demonstrates excellent results in the diagnosis of metastatic SCC in the head and neck with higher accuracy and greater reliability than FNAC.

Detection of radiation-induced lung injury in non-small cell lung cancer patients using hyperpolarized helium-3 magnetic resonance imaging.

PURPOSE: To compare hyperpolarized helium-3 magnetic resonance imaging ((3)He-MRI) acquired from non-small cell lung cancer (NSCLC) patients before and after external beam radiotherapy (EBRT). METHODS AND MATERIALS: In an Ethics Committee-approved prospective study, five patients with histologically confirmed NSCLC gave written informed consent to undergo computed tomography (CT) and (3)He-MR ventilation imaging 1 week prior to and 3 months after radiotherapy. Images were registered to pre-treatment CT using anatomical landmark-based rigid registration to enable comparison. Emphysema was graded from examination of the CT. MRI-defined ventilation was calculated as the intersection of (3)He-MRI and CT lung volume as a percentage of the CT lung volume for the whole lung and regions of CT-defined pneumonitis. RESULTS: On pre-treatment images, there was a significant correlation between the degree of CT-defined emphysema and (3)He-MRI whole lung ventilation (Spearman's rho=0.90, p=0.04). After radiation therapy, pneumonitis was evident on CT for 3/5 patients. For these cases, (3)He-MRI ventilation was significantly reduced within the regions of pneumonitis (pre: 94.1±2.2%, post: 73.7±4.7%; matched pairs Student's t-test, p=0.02, mean difference=20.4%, 95% confidence interval 6.3-34.6%). CONCLUSIONS: This work demonstrates the feasibility of detecting ventilation changes between pre- and post-treatment using hyperpolarized helium-3 MRI for patients with NSCLC. Pre-treatment, the degree of emphysema and (3)He-MRI ventilation were correlated. For three cases of radiation pneumonitis, (3)He-MRI ventilation changes between pre- and post-treatment imaging were consistent with CT evidence of radiation-induced lung injury.

Use of magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) in the morphological examination of rat and rabbit fetuses from embryo-fetal development studies.

Images of the fetal skeleton and soft tissues of the head can be acquired using micro-CT and MRI respectively. Preliminary work has shown that the image acquisition times of commercially available micro-CT and MRI instruments are now sufficiently short, whilst still providing adequate image resolution, to allow high quality imaging of fetuses from embryo-fetal development (EFD) studies. Bespoke fetus holders, which allow the imaging of multiple specimens in a single imaging "run", have been used to increase throughput. Protocols have been devised that incorporate these technologies into routine rat and rabbit fetal examination regimes. It is intended to undertake evaluations of these protocols, using number of fetuses that replicate those that would be expected from normal EFD studies. Incorporation of these technologies is anticipated to allow all soft tissue and skeletal examination data to be collected on the same day, markedly reducing the time taken to provide data for evaluation.

Assessment of hyperpolarized 3He lung MRI for regional evaluation of interventional therapy: a pilot study in pediatric cystic fibrosis.

PURPOSE: To determine whether regional changes in lung ventilation in a group of pediatric cystic fibrosis (CF) patients following a course of chest physiotherapy could be detected with (3)He MRI. MATERIALS AND METHODS: The reproducibility of lung ventilation volume measurements obtained with (3)He lung magnetic resonance imaging (MRI) was established in a group of five children with CF age 6-15 years. The same methodology was then used to evaluate whether standard chest physiotherapy (percussion and drainage) had any immediate effect on regional ventilated lung volumes in a further group of nine age-matched CF children (5-15 years). RESULTS: Global lung ventilation volumes remained the same within the limits of sensitivity derived from the reproducibility study; however, regional lung ventilation was observed to change in most patients after therapy. CONCLUSION: (3)He MRI can be successfully used in children with CF, and has the sensitivity to detect regional quantitative changes in lung ventilation following chest physiotherapy.

Ventricular mass index correlates with pulmonary artery pressure and predicts survival in suspected systemic sclerosis-associated pulmonary arterial hypertension.

OBJECTIVE: The ventricular mass index (VMI) has been proposed as a diagnostic tool for the assessment of patients with suspected pulmonary hypertension (PH). We hypothesized that in patients with SSc it may predict the presence or absence of PH. METHODS: Details of all consecutive SSc patients undergoing MRI and right heart catheterization were collected prospectively. Subsequently, the VMI for all patients was calculated, and further baseline data were collected. RESULTS: Data for 40 patients, 28 of whom were diagnosed with PH at rest (PH(REST)), were analysed. VMI correlated strongly with mean pulmonary artery pressure (mPAP; r = 0.79). Using a VMI threshold of 0.56, positive predictive value (PPV) for PH(REST) was 88% and negative predictive value (NPV) was 100%. Using a threshold of 0.7, PPV was found to be 100% and NPV 53%. Echocardiographically obtained tricuspid gradient (TG) also demonstrated a strong correlation with mPAP. Two-year survival in patients with VMI <0.7 and > or =0.7 was 91 and 43%, respectively (P < 0.001). CONCLUSION: VMI correlates well with mPAP in patients with SSc and may have a role in non-invasively excluding clinically significant PH in breathless SSc patients in whom echocardiographic screening has failed. Further study in larger groups of patients is justified.

An image acquisition and registration strategy for the fusion of hyperpolarized helium-3 MRI and x-ray CT images of the lung.

The purpose of this ethics committee approved prospective study was to evaluate an image acquisition and registration protocol for hyperpolarized helium-3 magnetic resonance imaging ((3)He-MRI) and x-ray computed tomography. Nine patients with non-small cell lung cancer (NSCLC) gave written informed consent to undergo a free-breathing CT, an inspiration breath-hold CT and a 3D ventilation (3)He-MRI in CT position using an elliptical birdcage radiofrequency (RF) body coil. (3)He-MRI to CT image fusion was performed using a rigid registration algorithm which was assessed by two observers using anatomical landmarks and a percentage volume overlap coefficient. Registration of (3)He-MRI to breath-hold CT was more accurate than to free-breathing CT; overlap 82.9 +/- 4.2% versus 59.8 +/- 9.0% (p < 0.001) and mean landmark error 0.75 +/- 0.24 cm versus 1.25 +/- 0.60 cm (p = 0.002). Image registration is significantly improved by using an imaging protocol that enables both (3)He-MRI and CT to be acquired with similar breath holds and body position through the use of a birdcage (3)He-MRI body RF coil and an inspiration breath-hold CT. Fusion of (3)He-MRI to CT may be useful for the assessment of patients with lung diseases.

Proton magnetic resonance imaging for assessment of lung function and respiratory dynamics.

Since many pulmonary diseases present with a variable regional involvement, modalities for assessment of regional lung function gained increasing attention over the last years. Together with lung perfusion and gas exchange, ventilation, as a result of the interaction of the respiratory pump and the lungs, is an indispensable component of lung function. So far, this complex mechanism is still mainly assessed indirectly and globally. A differentiation between the individual determining factors of ventilation would be crucial for precise diagnostics and adequate treatment. By dynamic imaging of the respiratory pump, the mechanical components of ventilation can be assessed regionally. Amongst imaging modalities applicable to this topic, magnetic resonance imaging (MRI), as a tool not relying on ionising radiation, is the most attractive. Recent advances in MRI technology have made it possible to assess diaphragmatic and chest wall motion, static and dynamic lung volumes, as well as regional lung function. Even though existing studies show large heterogeneity in design and applied methods, it becomes evident that MRI is capable to visualise pulmonary function as well as diaphragmatic and thoracic wall movement, providing new insights into lung physiology. Partly contradictory results and conclusions are most likely caused by technical limitations, limited number of studies and small sample size. Existing studies mainly evaluate possible imaging techniques and concentrate on normal physiology. The few studies in patients with lung cancer and emphysema already give a promising outlook for these techniques from which an increasing impact on improved and quantitative disease characterization as well as better patient management can be expected.

Single-scan acquisition of registered hyperpolarized (3)He ventilation and ADC images using a hybrid 2D gradient-echo sequence.

The pulse sequences for hyperpolarized (3)He lung MRI that have made the most clinical impact to date are 1) those that supply regional apparent diffusion coefficient (ADC) measurements, which provide insight into early emphysematous destruction of the alveoli in the lungs, and 2) high-resolution ventilation images that provide regional indicators of airway obstruction in obstructive airway disease, such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). In this work a hybrid 2D ADC-ventilation sequence was used with low flip angles to acquire both sets of data in the same breath-hold. The performance of the sequence was investigated in vivo in a healthy subject and a subject with mild emphysema, and compared with conventional 2D gradient-echo (GRE) (3)He ventilation and ADC imaging sequences. Acquisition of the ADC and ventilation images in one breath-hold provides ventilation images with equal or better SNR (approximately 20) and the same spatial resolution (3.75 mm x 3.3 mm in plane) with simultaneous accurate, high-resolution ADC images. The hybrid sequence offers a means of conserving gas by using two-thirds of the (3)He gas needed for separate ADC and ventilation exams, and saves the subject from having to perform an extra breath-hold. The data are inherently spatially and temporally registered, allowing quantitative cross-correlation between high-spatial-resolution ADC and ventilation data.

Nonrigid image registration for head and neck cancer radiotherapy treatment planning with PET/CT.

PURPOSE: Head and neck radiotherapy planning with positron emission tomography/computed tomography (PET/CT) requires the images to be reliably registered with treatment planning CT. Acquiring PET/CT in treatment position is problematic, and in practice for some patients it may be beneficial to use diagnostic PET/CT for radiotherapy planning. Therefore, the aim of this study was first to quantify the image registration accuracy of PET/CT to radiotherapy CT and, second, to assess whether PET/CT acquired in diagnostic position can be registered to planning CT. METHODS AND MATERIALS: Positron emission tomography/CT acquired in diagnostic and treatment position for five patients with head and neck cancer was registered to radiotherapy planning CT using both rigid and nonrigid image registration. The root mean squared error for each method was calculated from a set of anatomic landmarks marked by four independent observers. RESULTS: Nonrigid and rigid registration errors for treatment position PET/CT to planning CT were 2.77 +/- 0.80 mm and 4.96 +/- 2.38 mm, respectively, p = 0.001. Applying the nonrigid registration to diagnostic position PET/CT produced a more accurate match to the planning CT than rigid registration of treatment position PET/CT (3.20 +/- 1.22 mm and 4.96 +/- 2.38 mm, respectively, p = 0.012). CONCLUSIONS: Nonrigid registration provides a more accurate registration of head and neck PET/CT to treatment planning CT than rigid registration. In addition, nonrigid registration of PET/CT acquired with patients in a standardized, diagnostic position can provide images registered to planning CT with greater accuracy than a rigid registration of PET/CT images acquired in treatment position. This may allow greater flexibility in the timing of PET/CT for head and neck cancer patients due to undergo radiotherapy.