Optimal Imaging Protocol Research Articles

Particularities in differential diagnostics of epileptogenic brain malformations on the low-field MRI-device

Background.It has been suggested that the part of the cryptogenic epilepsies is a consequence of minor-foci disorders of cortical architectonics, the diagnosis of which is not always possible due to the unavailability of MR-scanners with high magnetic induction.Objective:determination of the best options of the low-field MRI-device for visualization of epileptogenic brain malformations in children with symptomatic focal forms of epilepsy.Materials and methods.Were analyzed MRI data of 24 children undergoing investigations regarding for difficult-to-treat or pharmacoresistant forms of focal epilepsy in the Department of Magnetic-Resonance Tomography, Central Children Clinical Hospital of FMB Agency of Russia at 2015–2017. All the patients underwent brain MRI according to standard routine protocol. Simultaneously we review conclusions of epileptologist and the preliminary video-electroencefalographic monitoring data for determination of the optimal imaging protocol for every specific form of epilepsy. For imaging of the epileptogenic brain lesion the MRI study was conducted on open-ended device “Aperto” (Hitachi Ltd., Japan) of static magnetic field with the tension characteristics of 0.4 T. The thickness of the slices and the scan step was performed at 3.0 and 3.5 mm (the maximum value of slice thickness and step due to the technical conditions of the used scanner without losing in signalto-noise ratio) with the use of special positioning of slices in the coronal and axial projections, T2, T1, STIR, FLAIR weighted images perpendicular and parallel to the long axis of the hippocampus.Results and conclusion.In 24 patients were revealed structural brain changes that have neuroradiological signs of brain malformations. In all the patients this changes were associated with difficult to treat and drug-resistant forms of focal epilepsy. The newly identified malformations were observed in 10 patients, and in 3 cases the changes detected after previous MRI (including high-field MRI-devices) whose results were false-negative. In 11 patients diffuse brain abnormalities had been revealed, including the combinations of several hypogenesis and dysplastic pathologies. In 13 patients were marked different types of hemispheric and regional disorders of cortical development including focal cortical dysplasia. Extensive unilateral and bilateral changes were clearly distinguishable on the routine MRI. The low-tension technique approximated to the epileptic scanning protocol in some cases allowed to assess the affected area and revealed the combination of different variants of pathological cortical organization. In 7 cases the preliminary diagnosis based on the results of previous MRI studies including high-field MRI-devices. In 2 of these patients this changes were minor-focal, not visualized according to the routine MRI protocol, and had the differentiation characteristics between focal cortical dysplasia IIb/dysembryoplastic neuroepithelial tumor/ganglioglioma types. Disappointing results of visualization of mesial-basal temporal lobe regions aimed to detect small-caliber intracortical formations were observed. These patients contained a separate group of 12 children for whom extensive investigation which includes high-field MRI scan protocol on epileptic program was recommended.

Classification of breast microcalcifications using dual-energy mammography.

The potential of dual-energy mammography for microcalcification classification was investigated with simulation and phantom studies. Classification of type I/II calcifications was performed using the tissue attenuation ratio as a performance metric. The simulation and phantom studies were carried out using breast phantoms of 50% fibroglandular and 50% adipose tissue composition and thicknessess ranging from 3 to 6cm. The phantoms included models of microcalcifications ranging in size between 200 and . The simulation study was carried out with fixed MGD of 1.5mGy using various low- and high-kVp spectra, aluminum filtration thicknesses, and exposure distribution ratios to predict an optimized imaging protocol for the phantom study. Attenuation ratio values were calculated for microcalcification signals of different types at two different voltage settings. ROC analysis showed that classification performance as indicated by the area under the ROC curve was always greater than 0.95 for 1.5mGy deposited mean glandular dose. This study provides encouraging first results in classifying malignant and benign microcalcifications based solely on dual-energy mammography images.

Diagnostic Performance of 4D CT and Sestamibi SPECT/CT in Localizing Parathyroid Adenomas in Primary Hyperparathyroidism.

Background There currently is no consensus on the optimal localization procedure and imaging protocol for parathyroid adenoma. Parathyroid four-dimensional (4D) CT has emerged as a promising method for preoperative localization. Purpose To evaluate the diagnostic performance of parathyroid 4D CT and technetium 99m-sestamibi (hereafter, referred to as sestamibi) SPECT/CT in preoperative localization in patients with primary hyperparathyroidism. Materials and Methods This was a single-institution retrospective study of patients with primary hyperparathyroidism who underwent a combined imaging protocol of sestamibi SPECT/CT and 4D CT (noncontrast, contrast agent-enhanced, arterial, and delayed venous phases) acquired in a single setting from February 2013 to May 2016, with subsequent parathyroidectomy within 6 months. Reference standard for correct localization was on the basis of location denoted on operative reports, with pathologic confirmation of parathyroid adenoma or hyperplasia. By using a four-quadrant analysis, sensitivity, specificity, and area under the curve (AUC) for localization of the hyperfunctioning parathyroid gland or glands at sestamibi SPECT/CT and 4D CT were compared, per modality and in combination. Results Four hundred patients (319 women, 81 men; mean age, 61 years ± 14 [standard deviation]) were evaluated. Similar diagnostic performance was found in both combined 4D CT with sestamibi SPECT/CT and 4D CT alone (area under the curve [AUC], 0.88 [95% CI: 0.86, 0.90] and 0.87 [95% CI: 0.85, 0.90], respectively; P = .82). Both modalities outperformed sestamibi SPECT/CT (AUC, 0.78; 95% CI: 0.76, 0.81; P < .001). Four-dimensional CT showed higher sensitivity than did sestamibi SPECT/CT (sensitivity, 79.3% [414 of 522] vs 58.0% [303 of 522], respectively; P < .001). In a subset analysis, 4D CT had higher sensitivity than sestamibi SPECT/CT in patients with single-gland disease (sensitivity, 92.5% [297 of 321] vs 75.1% [241 of 321], respectively; P < .001) and with multigland disease (sensitivity, 58.2% [117 of 201] vs 30.8% [62 of 201], respectively; P < .001). Conclusion Four-dimensional CT provided superior preoperative localization compared with sestamibi SPECT/CT in patients with single and multigland disease. The combination of the two modalities did not improve diagnostic performance compared with four-dimensional CT alone. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Sinha and Oates in this issue.

Abstract WP93: Inter-Operator Heterogeneity in CT/CTP-Guided Patient Selection for Thrombectomy

Introduction: Recent trials have shown application of CTP in identifying patients who will have a favorable response to endovascular reperfusion therapy, in both early and extended time windows after onset of stroke symptoms. However, the optimal imaging protocol to select these patients is still a matter of debate. The purpose of this study was to assess how CTP affects clinical decision making in different time periods after stroke and to investigate the inter-rater agreement in imaging interpretation. Methods: Imaging sets including non-contrast CT (NCCT) and CTP [RAPID (iSchemaView Inc, Menlo Park, CA)] from patients admitted with the diagnosis of large vessel occlusion (MCA and ICA) stroke at a single institution were retrospectively reviewed by five neurovascular interventionists independently. In order to focus upon the contribution of imaging to decision-making, interventionists were blinded to demographics and clinical symptoms of patients. Images were presented to each interventionist in random fashion, at separate settings (assessing decision-making within 0-6 and 6-24 hrs). Each interventionist was asked whether they would intervene first based upon NCCT, and then after viewing CTP images for the same patient. Results: Datasets of 38 consecutive patients (female/male: 14/24; mean age: 63.24; side of stroke left/right: 21/17; thrombectomy no/yes: 18/20) were reviewed. Inter-rater agreement was moderate for thrombectomy in both time windows (0-6 hrs: κ = 0.43; 6-24 hrs: κ = 0.50) based on NCCT. Interventionists had overall fair (κ = 0.33) versus moderate agreement (κ = 0.55) for thrombectomy based on CTP in 0-6 hrs versus 6-24 hrs time-windows, respectively. The proportion of times that CTP altered decision-making after viewing NCCT yielded only poor (κ = 0.17) and fair (κ = 0.24) agreement across interventionists in 0-6 and 6-24 hrs time-windows, respectively. Conclusions: We found heterogeneity in decision-making across neurointerventionists when using the same neuroimaging to determine whether to intervene in acute ischemic stroke, in both the 0-6 and 6-24 hrs time-windows. While overall agreement was higher in 6-24 hrs time window, our data may have important clinical ramifications in standardization of processes of care.

Improved Visualization of Juxtaprosthetic Tissue Using Metal Artifact Reduction Magnetic Resonance Imaging: Experimental and Clinical Optimization of Compressed Sensing SEMAC.

The purpose of this study was to identify an optimal imaging protocol for metal artifact reduced magnetic resonance imaging by application of different imaging and postprocessing parameters in compressed sensing slice-encoding for metal artifact correction (CS-SEMAC) and to test it in patients with total hip arthroplasty (THA). In an experimental setup, a phantom consisting of a standard THA embedded in gadolinium-containing agarose was scanned at 1.5 T. Pulse sequences included coronal short tau inversion recovery (STIR), T1-weighted (w), and T2-w CS-SEMAC sequences. All pulse sequences were acquired with 11, 19, and 27 slice-encoding steps (SESs), respectively. For each raw dataset, postprocessing was performed with variations of the parameters: (1) number of iterations (5, 10, 20, 30, 50) and (2) normalization factor (0.0005, 0.001, 0.002, 0.003, 0.005). Following, in clinical magnetic resonance scans of patients with THA, identical STIR, T1-w, and T2-w pulse sequences with 11 and 19 SESs were acquired and were postprocessed similarly with variations in parameters. Semiquantitative outcome measures were assessed on a 5-point scale (1 = best, 5 = worst). The overall best image quality was determined. Signal-to-noise ratio and contrast-to-noise ratio were calculated. Statistical analyses included descriptive statistics, t-tests, multivariate regression models, and partial Spearman correlations. Scan times varied between 2:24 (T2-w, 11 SESs) and 8:49 minutes (STIR, 27 SESs). Reconstruction times varied between 3:14 minutes (T1-w, 11 SESs, 5 iterations) and 85:00 minutes (T2-w, 27 SESs, 50 iterations). Signal-to-noise ratio and contrast-to-noise ratio increased with increasing SESs, iterations, and normalization factor. In phantom scans, artifact reduction was optimal with an intermediate normalization factor (0.001) and improved with higher SESs and iterations. However, iterations greater than 20 did not improve artifact reduction or image quality further. On the contrary, ripple artifacts increased with higher SESs and iterations. In clinical scans, up to 20 iterations reduced blurring of the image; no further reduction was observed with iterations greater than 20. A normalization factor of 0.001 or 0.002 was best for reduction of blurring, whereas the soft tissue contrast was better and the distortion of soft tissue was less severe with lower normalization factors. Overall best soft tissue image quality was found for STIR and T1-w images with 19 SESs, 10 iterations, and a normalization factor of 0.001, and for T2-w images with 11 SESs, 10 iterations, and a normalization factor of 0.0005. Optimized advanced acceleration and reconstruction algorithms of CS-SEMAC have been identified to reduce metal artifacts in patients with THA enabling imaging with clinically feasible acquisition and reconstruction times.

Clinical evaluation of CT radiation dose in whole-body 18F-FDG PET/CT in relation to scout imaging direction and arm position.

Radiation exposure in CT is modulated by automatic exposure control (AEC) mainly based on scout images. We evaluated CT radiation dose in whole-body PET/CT in relation to scout imaging direction and arm position, and investigated the behavior of AEC. Eighty adult patients who underwent whole-body 18F-FDG PET/CT were divided into groups A, B, C, and D. The posteroanterior scout image alone (PA scout) was used for AEC-based dose modulation in groups A and B, while the posteroanterior and lateral scout images (PA + Lat scout) were used in groups C and D. Patients in groups A and C were imaged with their arms beside the head, while those in groups B and D were imaged with their arms at the sides of the trunk. Dose-length product provided by the scanner was recorded. The tube current value, a determinant of radiation dose, for each slice was plotted against slice location to produce a tube current modulation curve. The scan range was divided into seven anatomical regions, and regional tube current was defined as average tube current for each region. Effective dose was calculated for each region and then summed together. Regional tube current was higher in the body trunk and proximal thigh using the PA scout than using the PA + Lat scout, resulting in higher dose-length product and effective dose using the PA scout. A marked dose increase was shown in the shoulder especially using the PA scout. Spike-like high current at the top of the head was often observed in tube current modulation curves using the PA scout but not using the PA + Lat scout. Raising the arms increased tube current in the head and neck and decreased it in the chest and abdomen. Although dose-length product did not differ significantly depending on arm position, raising the arms decreased effective dose significantly. AEC-based CT dose modulation in whole-body PET/CT is affected by scout imaging direction and arm position, which should be considered to determine an optimal imaging protocol for whole-body PET/CT.

Lateral geniculate nucleus volumetry at 3T and 7T: Four different optimized magnetic-resonance-imaging sequences evaluated against a 7T reference acquisition

PurposeThe lateral geniculate nucleus (LGN) is an essential nucleus of the visual pathway, occupying a small volume (60–160 mm3) among the other thalamic nuclei. The reported LGN volumes vary greatly across studies due to technical limitations and due to methodological differences of volume assessment. Yet, structural and anatomical alterations in ophthalmologic and neurodegenerative pathologies can only be revealed by a precise and reliable LGN representation. To improve LGN volume assessment, we first implemented a reference acquisition for LGN volume determination with optimized Contrast to Noise Ratio (CNR) and high spatial resolution. Next, we compared CNR efficiency and rating reliability of 3D Magnetization Prepared Rapid Gradient Echo (MPRAGE) images using white matter nulled (WMn) and grey matter nulled (GMn) sequences and its subtraction (WMn-GMn) relative to the clinical standard Proton Density Turbo Spin Echo (PD 2D TSE) and the reference acquisition. We hypothesized that 3D MPRAGE should provide a higher CNR and volume determination accuracy than the currently used 2D sequences. Materials and methodsIn 31 healthy subjects, we obtained at 3 and 7 T the following MR sequences: PD-TSE, MPRAGE with white/grey matter signal nulled (WMn/GMn), and a motion-corrected segmented MPRAGE sequence with a resolution of 0.4 × 0.4 × 0.4 mm3 (reference acquisition). To increase CNR, GMn were subtracted from WMn (WMn-GMn). Four investigators manually segmented the LGN independently. ResultsThe reference acquisition provided a very sharp depiction of the LGN and an estimated mean LGN volume of 124 ± 3.3 mm3. WMn-GMn had the highest CNR and gave the most reproducible LGN volume estimations between field strengths. Even with the highest CNR efficiency, PD-TSE gave inconsistent LGN volumes with the weakest reference acquisition correlation. The LGN WM rim induced a significant difference between LGN volumes estimated from WMn and GMn. WMn and GMn LGN volume estimations explained most of the reference acquisition volumes' variance. For all sequences, the volume rating reliability were good. On the other hand, the best CNR rating reliability, LGN volume and CNR correlations with the reference acquisition were obtained with GMn at 7 T. ConclusionWMn and GMn MPRAGE allow reliable LGN volume determination at both field strengths. The precise location and identification of the LGN (volume) can help to optimize neuroanatomical and neurophysiological studies, which involve the LGN structure. Our optimized imaging protocol may be used for clinical applications aiming at small nuclei volumetric and CNR quantification.

Assessment of Optimal Imaging Protocol Sequences After Laser-Induced Thermal Therapy for Intracranial Tumors.

Magnetic resonance-guided laser-induced thermal therapy (MRgLITT) is a novel, minimally invasive method currently being used to treat a wide range of intracranial pathologies. No accepted guidelines exist on what the appropriate magnetic resonance imaging (MRI) sequences are for evaluating short-term postablation changes, especially when patients are not able to receive gadolinium. To evaluate which MRI sequences provide the greatest inter-rater reliability and least amount of variability in assessment of ablation volume after MRgLITT for intracranial neoplasms. Twenty patients who received MRgLITT were included. Three raters calculated volumetric measurements on postprocedural axial spoiled gradient recalled (SPGR), fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and gradient echo (GRE) sequences. Measured volumes were analyzed using intraclass correlation to determine which protocol had the most concordance among the 3 raters. Postcontrast SPGR sequences were most concordant in our study, with an intraclass correlation of 0.981. DWI was the next-most concordant imaging sequence with an intraclass correlation of 0.958. The least concordant were GRE (0.895) and FLAIR (0.866) images. SPGR was also the least variable and had the most consistent volume ratings compared to the other sequences. This study is the first to evaluate the inter-rater reliability of different MRI sequence protocols in the context of post-MRgLITT volumetric evaluation. SPGR postcontrast images facilitate the greatest interobserver concordance when characterizing post-MRgLITT tumor appearance and volumetrics, with DWI ranked second. Based on our findings, SPGR sequences are likely to yield the highest degree of concordance in post-MRgLITT lesion evaluation. When gadolinium cannot be given, DWI should provide the next most reliable estimation.

NCCT and CTA-based imaging protocol for endovascular treatment selection in late presenting or wake-up strokes

IntroductionRecently, the benefit of selecting patients for endovascular treatment (EVT) beyond the 6-hour time window using a tissue-based approach was demonstrated in two randomized trials. The optimal imaging protocol for...

Optimizing Cardiac CTA Acquisition in Congenital Heart Disease

The purpose of this review of performance of cardiac computed tomographic angiography (CCTA) in patients with congenital heart disease (CHD) is to describe a strategy for optimizing CCTA protocols for various forms of CHD at diagnosis and throughout the lifetime of a patient. Recent expert consensus statements provide key recommendations for patient selection and technical performance of CCTA with tips to optimize contrast injection, scan acquisition, and understanding anatomy and postoperative changes in patients with CHD. Spectral CT will become invaluable in acquiring image data which has potential for enabling improved image quality and perhaps physiologic information. CCTA is an important non-invasive imaging modality for making initial diagnosis and providing follow-up imaging in patients of all ages with CHD. Optimization of imaging protocols requires combined expertise in all forms of CHD, surgical palliation procedures, and knowledge of surgical options for CHD surgery.

An optimized imaging protocol for orofacial cleft patients.

The objective was to present an optimized imaging protocol for orofacial cleft (OFC) patients, which might be used as an international recommendation for OFC care programs. The present radiological protocol has been structured by the OFC team of the University Hospitals Leuven based on a combined approach of clinical experience and scientific evidence. The development was based on careful monitoring of the existing needs for radiological diagnosis by the involved disciplines. Needs were revised by expert consensus and radiological optimization. Effective doses were converted to panoramic equivalents (professional conversion) and background radiation (patient conversion). At the age of 6, a panoramic radiograph is taken for the evaluation of dental anomalies. For the preoperative planning of secondary alveolar bone, grafting a low‐resolution cone beam computer tomography (CBCT) of a limited field of the maxilla is taken at the age of 7 to 9. At the age of 10, 15, and 20, a low‐resolution CBCT of both jaws with the smallest possible field is taken serving as conventional, presurgical, and end of treatment records, respectively. Two‐dimensional images are reconstructed out of 3D ones. There are currently no international guidelines concerning the imaging protocol for OFC patients. It is clear that a multidisciplinary approach plays a key role in radiation hygiene. In this article, we presented an optimized imaging protocol for OFC patients based on European guidelines to accomplish the concepts of justification and optimization, which might be used as an international recommendation for OFC care programs.

Three-dimensional radiological evaluation of secondary alveolar bone grafting in cleft lip and palate patients: a systematic review.

To systematically review the existing literature on the three-dimensional (3D) radiological evaluation of secondary alveolar bone grafting (SABG) in cleft lip and palate (CLP) patients, with specific interest in 3D imaging protocols and assessment methods. A comprehensive literature search on PubMed, Embase and the Cochrane Library wasconducted. Included publications concerned 3D imaging for evaluation of SABG in CLP patientswhile articles about primary or tertiary bone grafting or using of two-dimensional images only were excluded.Study quality was evaluated using the Methodological Index for Non-Randomized Studies or the Cochrane Collaboration tool for assessing risk of bias. The search yielded 1735 citations, of which 38 met the inclusion criteria. We noticed a large variability in imaging protocols and bone graft evaluation methods between studies. Most articles were observational studies with medium to low methodological quality, except for the one randomised clinical trial having a low risk of bias. There is a lack of prospective, controlled trials based on a consistent imaging protocol with a sufficiently long follow-up period. A pressing need exists for the development of a consistent optimized imaging protocol for diagnosis and followup of SABG in CLP patients. Although 3D evaluation methods seem to be more precise than two-dimensional methods, we should be careful when comparing theoutcomes arising from different 3D measuring techniques.

Multiple enface image averaging for enhanced optical coherence tomography angiography imaging.

To investigate the effect of multiple enface image averaging on image quality of the optical coherence tomography angiography (OCTA). Twenty-one normal volunteers were enrolled in this study. For each subject, one eye was imaged with 3×3mm scan protocol, and another eye was imaged with the 6×6mm scan protocol centred on the fovea using the ZEISS Angioplex™ spectral-domain OCTA device. Eyes were repeatedly imaged to obtain nine OCTA cube scan sets, and nine superficial capillary plexus (SCP) and deep capillary plexus (DCP) were individually averaged after registration. Eighteen eyes with a 3×3mm scan field and 14 eyes with a 6×6mm scan field were studied. Averaged images showed more continuous vessels and less background noise in both the SCP and the DCP as the number of frames used for averaging increased, with both 3×3 and 6×6mm scan protocols. The intensity histogram of the vessels dramatically changed after averaging. Contrast-to-noise ratio (CNR) and subjectively assessed image quality scores also increased as the number of frames used for averaging increased in all image types. However, the additional benefit in quality diminished when averaging more than five frames. Averaging only three frames achieved significant improvement in CNR and the score assigned by certified grades. Use of multiple image averaging in OCTA enface images was found to be both objectively and subjectively effective for enhancing image quality. These findings may of value for developing optimal OCTA imaging protocols for future studies.

Real-time speech MRI: Commercial Cartesian and non-Cartesian sequences at 3T and feasibility of offline TGV reconstruction to visualise velopharyngeal motion

PurposeThis study aims to improve clinical reliability of real-time Magnetic Resonance Imaging (rt-MRI) in the visualisation of velopharyngeal motion during speech. MethodsSeven subjects were imaged at 3T during natural phonation. Speech rt-MRI methodologies were investigated with (i) a comparison of commercial Cartesian and non-Cartesian (radial and spiral) rt-MRI sequences and (ii) investigation of further improvement with accelerated radial acquisition and offline reconstruction methodology. ResultsCartesian and non-Cartesian protocols were implemented with temporal resolutions between 10 frames per second (fps) and 27 fps and voxel sizes between 1.5 × 1.5 × 10 mm3 and 2.7 × 2.7 × 10 mm3. Commercial spiral acquisitions provided superior contrast-to-noise ratio (CNR) than otherwise equivalent Cartesian and radial. Spirals at 22 fps allowed for improved spatial resolution (1.9 × 1.9 mm2) when compared to similar Cartesian protocols (20 fps), limited to a lower spatial resolution (2.7 × 2.7 mm2). Cartesian protocols were on average scored higher than spiral protocols in visual quality. However, some variability was found on choice of recommended imaging protocol between subjects. Accelerated radial data reconstructed offline with a Total Generalized Variation (TGV) scheme showed improved visual sharpness of velum motion. Discussion/ConclusionAdequate visualisation of velopharyngeal motion with commercial rt-MRI at 3T was possible. Both Cartesian and spiral protocols demonstrated adequate temporal depiction and overall image quality. However, choice of optimal imaging protocol at 3T was more subject-dependent than in previously published 1.5T data and additional care should be taken when selecting an adequate protocol. Offline TGV reconstruction of radial data has shown potential to improve temporal sharpness.

Optimized Longitudinal Monitoring of Stem Cell Grafts in Mouse Brain Using a Novel Bioluminescent/Near Infrared Fluorescent Fusion Reporter

Biodistribution and fate of transplanted stem cells via longitudinal monitoring has been successfully achieved in the last decade using optical imaging. However, sensitive longitudinal imaging of transplanted stem cells in deep tissue like the brain remains challenging not only due to low light penetration but because of other factors such as low or inferior expression levels of optical reporters in stem cells and stem cell death after transplantation. Here we describe an optimized imaging protocol for sensitive long-term monitoring of bone marrow-derived human mesenchymal stem cells (hMSCs) expressing a novel bioluminescent/near infrared fluorescent (NIRF) fusion reporter transplanted in mouse brain cortex. Lentivirus expressing the luc2-iRFP720 reporter, a fusion between luc2 codon-optimized firefly luciferase (luc2) and the gene encoding NIRF protein iRFP720, was generated to transduce hMSCs. These cells were analyzed for their fluorescent and bioluminescent emission and checked for their differentiation potential. In vivo experiments were performed by transplanting decreasing amounts of luc2-iRFP720 expressing hMSCs in mouse brain, followed by fluorescence and bioluminescence imaging (BLI) starting 1 wk after cell injection when the blood–brain barrier was restored. Bioluminescent images were acquired when signals peaked and used to compare different luc2 substrate performances, that is, D-luciferin (D-Luc; 25 μM/kg or 943 μM/kg) or CycLuc1 (25 μM/kg). Results showed that luc2-iRFP720 expressing hMSCs maintained a good in vitro differentiation potential toward adipocytes, chondrocytes, and osteocytes, suggesting that lentiviral transduction did not affect cell behavior. Moreover, in vivo experiments allowed us to image as low as 1 × 105 cells using both fluorescence and BLI. The highest bioluminescent signals (∼1 × 107 photons per second) were achieved 15 min after the injection of D-Luc (943 μM/kg). This allowed us to monitor as low as 1 × 105 hMSCs for the subsequent 7 wk without a significant drop in bioluminescent signals, suggesting the sustained viability of hMSCs transplanted into the cortex.

Paramagnetic 19F Relaxation Enhancement in Nickel(II) Complexes of N-Trifluoroethyl Cyclam Derivatives and Cell Labeling for 19F MRI.

1,8-Bis(2,2,2-trifluoroethyl)cyclam (te2f) derivatives with two coordinating pendant arms involving methylenecarboxylic acid (H2te2f2a), methylenephosphonic acid (H4te2f2p), (2-pyridyl)methyl (te2f2py), and 2-aminoethyl arms (te2f2ae) in 4,11-positions were prepared, and their nickel(II) complexes were investigated as possible 19F MR tracers. The solid-state structures of several synthetic intermediates, ligands, and all complexes were confirmed by X-ray diffraction analysis. The average Ni···F distances were determined to be about 5.2 Å. All complexes exhibit a trans-III cyclam conformation with pendant arms bound in the apical positions. Kinetic inertness of the complexes is increased in the ligand order te2f2ae ≪ te2f < te2f2py ≈ H4te2f2p ≪ H2te2f2a. The [Ni(te2f2a)] complex is the most kinetically inert Ni(II) complex reported so far. Paramagnetic divalent nickel caused a shortening of 19F NMR relaxation time down to the millisecond range. Solubility, stability, and cell toxicity were only satisfactory for the [Ni(te2f2p)]2- complex. This complex was visualized by 19F MRI utilizing an ultrashort echo time (UTE) imaging pulse sequence, which led to an increase in sensitivity gain. Mesenchymal stem cells were successfully loaded with the complex (up to 0.925/5.55 pg Ni/F per cell).19F MRI using a UTE pulse sequence provided images with a good signal-to-noise ratio within the measurement time, as short as tens of minutes. The data thus proved a major sensitivity gain in 19F MRI achieved by utilization of the paramagnetic (transition) metal complex as 19F MR tracers coupled with the optimal fast imaging protocol.

Radiation Risk Versus Projected Clinical Benefit of Surveillance Imaging for Early Detection and Treatment of Breast Cancer Metastases

To assess the expected radiation risk versus outcomes benefit of adding multimodality surveillance imaging to standard follow-up care for breast cancer patients at high risk (>30%) for developing future metastases. We first sought to determine an optimal follow-up surveillance imaging protocol for detecting metastatic breast cancer (MBC) while yet in an OligoMBC state (≤6 lesions). Coumans et al. deduced that the average doubling time (DT) for distant metastases (DM) to any site is 1.7 months. Using this, the time to first detection under MRI and CT would be expected to precede the time to first clinical symptoms of a DM by ≥2 years. Using the findings of Newton et al., the majority of patients will develop imaging-detectable metastases within 3.5 years of diagnosis of their primary tumor, with the highest yearly frequency of detections in each of the first 2 years. The ideal imaging protocol would use an initial scan at 9 months after treatment of the primary tumor, with repeated 9-month follow-up scans out to 45 months (3.75 years). The proposed protocol involves 5 PET/CT body scans over 3.75 years, with 91 mSv of total exposure. The following risk/benefit assessment assumes a 30% incidence of MBC for the stage II-III BC survivors in the imaging study and a 5-year OS of 47% for OligoMBC, 10.7% for non-OligoMBC, and 20% for overall MBC. The prevalence of OligoMBC is currently about 22% and is projected to be >60% under the surveillance imaging protocol. Using these values, under standard of care follow-up, 76% of high-risk women would be surviving at 5 years (70% without MBC + 20% survival in the remaining 30%). With imaging, this increases to 79.75% (70% without MBC + 12%*10.7% +18%*47%), creating a 3.75% OS benefit at 5 years when imaging is included in follow-up care. If 1,351 high-risk patients were enrolled in this study, 1 patient would be expected to die from cancer induced by the 5 PET/CT scans sometime during her lifetime (based on a 0.074% lifetime cancer mortality), while 51 patients would be alive at 5 years beyond the project period that would otherwise have succumbed to MBC within that time frame. We deduced a 51:1 survival benefit-to-cost ratio for adding surveillance imaging for detection and treatment of early metastases in high-risk BC survivors. The recommended imaging protocol entails imaging every 9 months for 3.75 years (5 scans total) using brain MRI and PET/CT. We are currently performing a pilot study to prospectively assess these study findings.

Optimization of imaging protocols for myocardial blood flow (MBF) quantification with 18F-flurpiridaz PET

The new PET tracer, 18F-flurpiridaz, with high myocardial extraction allows quantitative myocardial blood flow (MBF) estimation from dynamic PET data and tracer kinetic modeling. The goal of this study is to determine the optimal imaging protocols and parameters using a realistic simulation study. The time activity curves (TACs) of different tissue organs from a 30-s infusion time (IT) of 18F-flurpiridaz in a dynamic PET study were extracted from a previous study. The TACs at different time points were incorporated in a series of realistic 3D XCAT phantoms from which the parameters of a 2-compartment model and the ‘true’ MBF of 18F-flurpiridaz were determined. The compartmental model was used to generate TACs from 7 additional ITs. PET projection data from the XCAT phantoms were generated using Monte Carlo simulation. They were reconstructed using an OS-EM reconstruction algorithm with different update number (N) to obtain dynamic PET images. The blood and myocardial TACs were derived from the dynamic images from which the MBF and %MBF error was estimated. The %MBF error decreases with increasing N of the OS-EM and levels off after ∼42. The 30-s IT gave the smallest %MBF error that decreases from ∼0.57% to ∼19.40%. The MBF for 2-min, 4-min, 8-min and 16-min IT were statistically significant different from the MBF for 30-s IT (P<0.05). Too fast or too slow infusion time gave higher %MBF error. The optimal imaging protocol in dynamic 18F-flurpiridaz PET for accurate quantitative MBF estimation was 30-s IT and N of ∼42 for the OS-EM.

Performance characteristics of magnetic resonance imaging without contrast agents or sedation in pediatric appendicitis.

Magnetic resonance imaging (MRI) has emerged as a promising modality for evaluating pediatric appendicitis. However optimal imaging protocols, including roles of contrast agents and sedation, have not been established and diagnostic criteria have not been fully evaluated. To investigate performance characteristics of rapid MRI without contrast agents or sedation in the diagnosis of pediatric appendicitis. We included patients ages 4-18years with suspicion of appendicitis who underwent rapid MRI between October 2013 and March 2015 without contrast agent or sedation. After two-radiologist review, we determined performance characteristics of individual diagnostic criteria and aggregate diagnostic criteria by comparing MRI results to clinical outcomes. We used receiver operating characteristic (ROC) curves to determine cut-points for appendiceal diameter and wall thickness for optimization of predictive power, and we calculated area under the curve (AUC) as a measure of test accuracy. Ninety-eight MRI examinations were performed in 97 subjects. Overall, MRI had a 94% sensitivity, 95% specificity, 91% positive predictive value and 97% negative predictive value. Optimal cut-points for appendiceal diameter and wall thickness were ≥7mm and ≥2mm, respectively. Independently, those cut-points produced sensitivities of 91% and 84% and specificities of 84% and 43%. Presence of intraluminal fluid (30/33) or localized periappendiceal fluid (32/33) showed a significant association with acute appendicitis (P<0.01), with sensitivities of 91% and 97% and specificities of 60% and 50%. For examinations in which the appendix was not identified by one or both reviewers (23/98), the clinical outcome was negative. Rapid MRI without contrast agents or sedation is accurate for diagnosis of pediatric appendicitis when multiple diagnostic criteria are considered in aggregate. Individual diagnostic criteria including optimized cut-points of ≥7mm for diameter and ≥2mm for wall thickness demonstrate high sensitivities but relatively low specificities. Nonvisualization of the appendix favors a negative diagnosis.

Four-Dimensional Phase Contrast Magnetic Resonance Imaging Protocol Optimization Using Patient-Specific 3-Dimensional Printed Replicas for InVivo Imaging Before and After Flow Diverter Placement.

Hemodynamics in cerebral aneurysms are currently investigated toward clinical efficacy using nonstandardized computational simulation techniques. At the same time, flow patterns and velocities are accessible by 4-dimensional phase contrast magnetic resonance imaging (4D pcMRI). Complexity of protocol design and imaging duration has limited the use of this technique in clinical imaging. A new approach is presented to overcome these limitations. Three-dimensional (3D) replicas of 2 cerebral aneurysms were fabricated by fused deposition prototyping (3D printing) and imaged using 4D pcMRI while connected to a magnetic resonance imaging-compatible continuous flow loop. Acquisition parameters were optimized with imaging times not to exceed 10 minutes. Six patients harboring cerebral aneurysms with sizes ranging from 4.7 to 13.8 mm were imaged with the optimized 4D pcMRI protocol. After treatment with the pipeline embolization device (PED), 4D pcMRI examinations were repeated in 3 patients. In all cases, major flow patterns were visualized well; smaller aneurysms posed a challenge because of limited spatial resolution, whereas larger aneurysms contained regions of low velocity resulting in limited contrast in the flow-sensitive images. After PED placement, ordered aneurysmal flow was disrupted and intra-aneurysmal velocity was reduced on average by 24.5% (range, 12.9-31.5%). Exploratory statistical analysis yielded a positive significant correlation (P < 0.01) between changes in inflow velocity and posttreatment intra-aneurysmal flow velocity. 4D pcMRI flow imaging in cerebral aneurysms within a time frame suitable for clinical imaging applications is feasible with optimized acquisition parameters, thereby enabling quantification of intra-aneurysmal flow changes after flow diverter device treatment.