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.

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.

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.

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.

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.

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.

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.

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.

Feasibility of image registration and intensity-modulated radiotherapy planning with hyperpolarized helium-3 magnetic resonance imaging for non-small-cell lung cancer.

PURPOSE: To demonstrate the feasibility of registering hyperpolarized helium-3 magnetic resonance images ((3)He-MRI) to X-ray computed tomography (CT) for functionally weighted intensity-modulated radiotherapy (IMRT) planning. METHODS AND MATERIALS: Six patients with non-small-cell lung cancer underwent (3)He ventilation MRI, which was fused with radiotherapy planning CT using rigid registration. Registration accuracy was assessed using an overlap coefficient, calculated as the proportion of the segmented (3)He-MR volume (V(MRI)) that intersects the segmented CT lung volume expressed as a percentage of V(MRI). For each patient, an IMRT plan that minimized the volume of total lung receiving a dose > or = 20 Gy (V(20)) was compared with a plan that minimized the V(20) to well-ventilated lung defined by the registered (3)He-MRI. RESULTS: The (3)He-MRI and CT were registered with sufficient accuracy to enable functionally guided IMRT planning (median overlap, 89%; range, 72-97%). In comparison with the total lung IMRT plans, IMRT constrained with (3)He-MRI reduced the V(20) not only for the well-ventilated lung (median reduction, 3.1%; range, 0.4-5.1%; p = 0.028) but also for the total lung volume (median reduction, 1.6%; range, 0.2-3.7%; p = 0.028). CONCLUSIONS: Statistically significant improvements to IMRT plans are possible using functional information provided by (3)He-MRI that has been registered to radiotherapy planning CT.

Rapid lung volumetry using ultrafast dynamic magnetic resonance imaging during forced vital capacity maneuver: correlation with spirometry.

INTRODUCTION: Dynamic magnetic resonance imaging (MRI) has the potential for rapid noninvasive evaluation of changes in lung volume. The aim of this study was to perform rapid lung volumetry using ultrafast dynamic MRI to capture a forced vital capacity (FVC) maneuver. MATERIALS AND METHODS: Nine healthy volunteers underwent 2-dimensional spoiled gradient echo imaging in coronal and sagittal planes during FVC maneuvers. An elliptical model of the axial cross section of the lungs was used to generate rapid volume-time curves. Spirometric indices were correlated with MR volumetry findings. RESULTS: Total lung volume calculated from static MRI correlated well with the dynamic MR scans (r = 0.83; P < 0.01). Spirometric indices (first second of forced expiration and FVC) calculated from our MR volumetry technique correlated well with conventional spirometry (P < 0.01). CONCLUSION: The technique provides a means of sampling lung volume change during the rapid subsecond movements that take place during a FVC maneuver.

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.

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.

Steady-state free precession with hyperpolarized 3He: experiments and theory.

The magnetization response of hyperpolarized 3He gas to a steady-state free precession (SSFP) sequence was simulated using matrix product operators. The simulations included the effects of flip angle (alpha), sequence timings, resonant frequency, gas diffusion coefficient, imaging gradients, T1 and T2. Experiments performed at 1.5 T, on gas phantoms and with healthy human subjects, confirm the predicted theory, and indicate increased SNR with SSFP through use of higher flip angles when compared to optimized spoiled gradient echo (SPGR). Simulations and experiments show some compromise to the SNR and some point spread function broadening at high alpha due to the incomplete refocusing of transverse magnetization, caused by diffusion dephasing from the readout gradient. Mixing of gas polarization levels by diffusion between slices is also identified as a source of signal loss in SSFP at higher alpha through incomplete refocusing. Nevertheless, in the sample experiments, a SSFP sequence with an optimized flip angle of alpha=20 degrees, and 128 sequential phase encoding views, showed a higher SNR when compared to SPGR (alpha=7.2 degrees) with the same bandwidth. Some of the gas sample experiments demonstrated a transient signal response that deviates from theory in the initial phase. This was identified as being caused by radiation damping interactions between the large initial transverse magnetization and the high quality factor (Q=250) birdcage resonator. In 3He NMR experiments, performed without imaging gradients, diffusion dephasing can be mitigated, and the effective T2 is relatively long (1 s). Under these circumstances the SSFP sequence behaves like a CPMG sequence with sinalpha/2 weighting of SNR. Experiments and simulations were also performed to characterize the off-resonance behaviour of the SSFP HP 3He signal. Characteristic banding artifacts due to off-resonance harmonic beating were observed in some of the in vivo SSFP images, for instance in axial slices close to the diaphragm where B0 inhomogeneity is highest. Despite these artifacts, a higher SNR was observed with SSFP in vivo when compared to the SPGR sequence. The trends predicted by theory of increasing SSFP SNR with increasing flip angle were observed in the range alpha=10-20 degrees without compromise to image quality through blurring caused by excessive k-space filtering.

Measurements and modeling of long range 3He diffusion in the lung using a "slice-washout" method.

In healthy lung tissue, pulsed-gradient-spin-echo (PGSE) methods reveal apparent diffusion coefficients (ADC) of the order 0.20 cm2 s(-1); for diffusion times of approximately 2 ms. For these short diffusion times the ADC is only sensitive to structures approximately (2Dt)1/2 approximately 0.6mm in size. Recent work, using magnetic tagging of the longitudinal magnetization has revealed much smaller ADC values for longer length scales. In this work, the in vivo ADC from within the air-spaces, was measured using a new technique. The signal from a series of images was analyzed from a slice that was repeatedly imaged. Diffusion tends to "top-up" the non-renewable polarization within the slice, which leads to a non-exponential decay in image signal. Image data were compared to 1D finite-difference simulations of diffusion to calculate a long range ADC value. The results yield values of the order 0.034 cm2 s(-1), which are nearly an order of magnitude smaller than those reported by PGSE measurements at shorter diffusion times.

Emphysematous changes and normal variation in smokers and COPD patients using diffusion 3He MRI.

INTRODUCTION: This study aims to quantify global and regional changes of diffusive motion of 3He gas within the lung, as determined by hyperpolarized 3He MR apparent diffusion coefficient (ADC) measurement, in non-smokers, smokers and chronic obstructive pulmonary disease (COPD) patients. METHODS: Age-matched groups of six healthy non-smokers, five healthy smokers and five patients with COPD. The experiments were performed with approval from the local Research Ethics Committee. Diffusion imaging was performed following hyperpolarized 3He gas inhalation, producing ADC maps. Mean and standard deviation of the ADCs were used to compare the subject groups and assess regional variations within individuals. RESULTS: The intra-individual standard deviation of ADC in the healthy smokers was significantly larger than that of the non-smoking group (P < 0.02). Compared to the non-smoking group, COPD patients had significantly higher mean and standard deviation of ADC (P < 0.01). The mean ADC in the anterior half of the chest was systematically higher than in the posterior half in the healthy non-smoking subject group. DISCUSSION: This study suggests that there are regional trends in the ADC values of healthy volunteers that may have implications for the clinical interpretation of ADC values. Less homogeneous ADC values have been detected in asymptomatic smokers, indicative of damage to the distal air spaces.

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.

Investigating 3He diffusion NMR in the lungs using finite difference simulations and in vivo PGSE experiments.

Finite difference simulations have been used to model (3)He gas diffusion in simulated lung tissue. The technique has the advantage that a wide range of structural models and diffusion-sensitizing gradient waveforms can be investigated, for which analytical methods would otherwise be virtually impossible. Results from simulations and in vivo pulsed-gradient-spin-echo (PGSE) experiments show that the apparent diffusion coefficient (ADC) is a function of diffusion time and gradient strength, and suggests diffusion is locally anisotropic. The simulations have been compared to recent work on an analytical model that characterizes lung tissue as a series of independent cylinders. The results presented may have clinical implications for (3)He ADC measurements in assessing lung diseases such as chronic-obstructive-pulmonary-disease.

Pediatric head and neck lesions: assessment of vascularity by MR digital subtraction angiography.

BACKGROUND AND PURPOSE: Pediatric head and neck lesions can be difficult to characterize on clinical grounds alone. We investigated the use of dynamic MR digital subtraction angiography as a noninvasive adjunct for the assessment of the vascularity of these abnormalities. METHODS: Twelve patients (age range, 2 days to 16 years) with known or suspected vascular abnormalities were studied. Routine MR imaging, time-of-flight MR angiography, and MR digital subtraction angiography were performed in all patients. The dynamic sequence was acquired in two planes at one frame per second by using a thick section (6-10 cm) selective radio-frequency spoiled fast gradient-echo sequence and an IV administered bolus of contrast material. The images were subtracted from a preliminary mask sequence and viewed as a video-inverted cine loop. RESULTS: In all cases, MR digital subtraction angiography was successfully performed. The technique showed the following: 1) slow flow lesions (two choroidal angiomas, eyelid hemangioma, and scalp venous malformation); 2) high flow lesions that were not always suspected by clinical examination alone (parotid hemangioma, scalp, occipital, and eyelid arteriovenous malformations plus a palatal teratoma); 3) a hypovascular tumor for which a biopsy could be safely performed (Burkitt lymphoma); and 4) a hypervascular tumor of the palate (cystic teratoma). CONCLUSION: Our early experience suggests that MR digital subtraction angiography can be reliably performed in children of all ages without complication. The technique provided a noninvasive assessment of the vascularity of each lesion that could not always have been predicted on the basis of clinical examination or routine MR imaging alone.