Automated multiclass segmentation, quantification, and visualization of the diseased aorta on hybrid PET/CT-SEQUOIA.

BACKGROUND: Cardiovascular disease is the most common cause of death worldwide, including infection and inflammation related conditions. Multiple studies have demonstrated potential advantages of hybrid positron emission tomography combined with computed tomography (PET/CT) as an adjunct to current clinical inflammatory and infectious biochemical markers. To quantitatively analyze vascular diseases at PET/CT, robust segmentation of the aorta is necessary. However, manual segmentation is extremely time-consuming and labor-intensive. PURPOSE: To investigate the feasibility and accuracy of an automated tool to segment and quantify multiple parts of the diseased aorta on unenhanced low-dose computed tomography (LDCT) as an anatomical reference for PET-assessed vascular disease. METHODS: A software pipeline was developed including automated segmentation using a 3D U-Net, calcium scoring, PET uptake quantification, background measurement, radiomics feature extraction, and 2D surface visualization of vessel wall calcium and tracer uptake distribution. To train the 3D U-Net, 352 non-contrast LDCTs from (2-[18F]FDG and Na[18F]F) PET/CTs performed in patients with various vascular pathologies with manual segmentation of the ascending aorta, aortic arch, descending aorta, and abdominal aorta were used. The last 22 consecutive scans were used as a hold-out internal test set. The remaining dataset was randomly split into training (n = 264; 80%) and validation (n = 66; 20%) sets. Further evaluation was performed on an external test set of 49 PET/CTs. The dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to assess segmentation performance. Automatically obtained calcium scores and uptake values were compared with manual scoring obtained using clinical softwares (syngo.via and Affinity Viewer) in six patient images. intraclass correlation coefficients (ICC) were calculated to validate calcium and uptake values. RESULTS: Fully automated segmentation of the aorta using a 3D U-Net was feasible in LDCT obtained from PET/CT scans. The external test set yielded a DSC of 0.867 ± 0.030 and HD of 1.0 [0.6-1.4] mm, similar to an open-source model with a DSC of 0.864 ± 0.023 and HD of 1.4 [1.0-1.8] mm. Quantification of calcium and uptake values were in excellent agreement with clinical software (ICC: 1.00 [1.00-1.00] and 0.99 [0.93-1.00] for calcium and uptake values, respectively). CONCLUSIONS: We present an automated pipeline to segment the ascending aorta, aortic arch, descending aorta, and abdominal aorta on LDCT from PET/CT and to accurately provide uptake values, calcium scores, background measurement, radiomics features, and a 2D visualization. We call this algorithm SEQUOIA (SEgmentation, QUantification, and visualizatiOn of the dIseased Aorta) and is available at https://github.com/UMCG-CVI/SEQUOIA. This model could augment the utility of aortic evaluation at PET/CT studies tremendously, irrespective of the tracer, and potentially provide fast and reliable quantification of cardiovascular diseases in clinical practice, both for primary diagnosis and disease monitoring.

How Often Do We Fail to Classify the Treatment Response with [18F]FDG PET/CT Acquired on Different Scanners? Data from Clinical Oncological Practice Using an Automatic Tool for SUV Harmonization.

PURPOSE: Tumor response evaluated by 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) with standardized uptake value (SUV) is questionable when pre- and post-treatment PET/CT are acquired on different scanners. The aims of our study, performed in oncological patients who underwent pre- and post-treatment [18F]FDG PET/CT on different scanners, were (1) to evaluate whether EQ·PET, a proprietary SUV inter-exams harmonization tool, modifies the EORTC tumor response classification and (2) to assess which classification (harmonized and non-harmonized) better predicts clinical outcome. PROCEDURES: We retrospectively identified 95 PET pairs (pre- and post-treatment) performed on different scanners (Biograph mCT, Siemens; GEMINI GXL, Philips) in 73 oncological patients (52F; 57.8 ± 16.3 years). An 8-mm Gaussian filter was applied for the Biograph protocol to meet the EANM/EARL harmonization standard; no filter was needed for GXL. SUVmax and SUVmaxEQ of the same target lesion in the pre- and post-treatment PET/CT were noted. For each PET pair, the metabolic response classification (responder/non-responder), derived from combining the EORTC response categories, was evaluated twice (with and without harmonization). In discordant cases, the association of each metabolic response classification with final clinical response assessment and survival data (2-year disease-free survival, DFS) was assessed. RESULTS: On Biograph, SUVmaxEQ of all target lesions was significantly lower (p = 0.001) than SUVmax (8.5 ± 6.8 vs 12.5 ± 9.6; - 38.6 %). A discordance between the two metabolic response classifications (harmonized and non-harmonized) was found in 19/95 (20 %) PET pairs. In this subgroup (n = 19; mean follow-up, 33.9 ± 9 months), responders according to harmonized classification (n = 9) had longer DFS (47.5 months, 88.9 %) than responders (n = 10) according to non-harmonized classification (26.3 months, 50.0 %; p = 0.01). Moreover, harmonized classification showed a better association with final clinical response assessment (17/19 PET pairs). CONCLUSIONS: The harmonized metabolic response classification is more associated with the final clinical response assessment, and it is able to better predict the DFS than the non-harmonized classification. EQ·PET is a useful harmonization tool for evaluating metabolic tumor response using different PET/CT scanners, also in different departments or for multicenter studies.

Evaluation of the impact of strain correction on the orientation of cardiac diffusion tensors with in vivo and ex vivo porcine hearts.

PURPOSE: To evaluate the importance of strain-correcting stimulated echo acquisition mode echo-planar imaging cardiac diffusion tensor imaging. METHODS: Healthy pigs (n = 11) were successfully scanned with a 3D cine displacement-encoded imaging with stimulated echoes and a monopolar-stimulated echo-planar imaging diffusion tensor imaging sequence at 3 T during diastasis, peak systole, and strain sweet spots in a midventricular short-axis slice. The same diffusion tensor imaging sequence was repeated ex vivo after arresting the hearts in either a relaxed (KCl-induced) or contracted (BaCl2 -induced) state. The displacement-encoded imaging with stimulated echoes data were used to strain-correct the in vivo cardiac diffusion tensor imaging in diastole and systole. The orientation of the primary (helix angles) and secondary (E2A) diffusion eigenvectors was compared with and without strain correction and to the strain-free ex vivo data. RESULTS: Strain correction reduces systolic E2A significantly when compared without strain correction and ex vivo (median absolute E2A = 34.3° versus E2A = 57.1° (P = 0.01), E2A = 60.5° (P = 0.006), respectively). The systolic distribution of E2A without strain correction is closer to the contracted ex vivo distribution than with strain correction, root mean square deviation of 0.027 versus 0.038. CONCLUSIONS: The current strain-correction model amplifies the contribution of microscopic strain to diffusion resulting in an overcorrection of E2A. Results show that a new model that considers cellular rearrangement is required. Magn Reson Med 79:2205-2215, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

The consistency of myocardial strain derived from heart deformation analysis.

The purpose of this study was to assess the consistency of semi-automated myocardial strain analysis by prototype software across field strengths, temporal resolutions, and examinations. 35 volunteers (48 ± 13 years; 20% women) and 25 patients (54 ± 12 years; 44% women) without significant cardiac dysfunction underwent cine cardiac magnetic resonance imaging (CMR) at 1.5 T with a temporal resolution of 39.2 msec. 34 subjects also underwent imaging at 3.0 T; 16 had repeat examinations within 14 days; and 9 underwent CMR with temporal resolutions of 12.5 and 39.2 msec on the same day. Prototype heart deformation analysis (HDA) software was used to retrospectively quantify strain from segmented balanced steady state free precession (bSSFP) cinegraphic images. Myocardial contours were automatically generated on short axis images and drawn at end-diastole by two independent reviewers on long-axis images. Contours were automatically propagated throughout the cardiac cycle. Global and regional peak systolic strain were compared across observers, field strengths, temporal resolutions, and examinations. Inter-observer agreement was excellent (ICC > 0.87, p < 0.01). Inter-examination variability was low, ranging from 1.7 (1.0-2.4)% to 2.5 (1.9-3.1)%, except for radial strain: 9.2 (7.6-10.5)%. Most global and regional strain values were not significantly different across field strengths and temporal resolutions (p > 0.05). Normal global peak systolic strain values with HDA were -25.0 (-24.0 to -26.1)% (LV circumferential), 60.5 (55.3 to 65.6)% (LV radial), -22.3 (-20.5 to - 24.0)% (LV longitudinal), and -26.0 (-23.8 to -28.2)% (RV longitudinal). HDA prototype software enabled efficient and consistent quantification of myocardial strain from conventional bSSFP cine CMR data, demonstrating clinical feasibility.

Effect of inversion time on the precision of myocardial late gadolinium enhancement quantification evaluated with synthetic inversion recovery MR imaging.

OBJECTIVES: To evaluate the influence of inversion time (TI) on the precision of myocardial late gadolinium enhancement (LGE) quantification using synthetic inversion recovery (IR) imaging in patients with myocardial infarction (MI). METHODS: Fifty-three patients with suspected prior MI underwent 1.5-T cardiac MRI with conventional magnitude (MagIR) and phase-sensitive IR (PSIR) LGE imaging and T1 mapping at 15 min post-contrast. T1-based synthetic MagIR and PSIR images were calculated with a TI ranging from -100 to +150 ms at 5-ms intervals relative to the optimal TI (TI0). LGE was quantified using a five standard deviation (5SD) and full width at half-maximum (FWHM) thresholds. Measurements were compared using one-way analysis of variance. RESULTS: The MagIRsy technique provided precise assessment of LGE area at TIs ≥ TI0, while precision was decreased below TI0. The LGE area showed significant differences at ≤ -25 ms compared to TI0 using 5SD (P < 0.001) and at ≤ -65 ms using the FWHM approach (P < 0.001). LGE measurements did not show significant difference over the analysed TI range in the PSIRsy images using either of the quantification methods. CONCLUSIONS: T1 map-based PSIRsy images provide precise quantification of MI independent of TI at the investigated time point post-contrast. MagIRsy-based MI quantification is precise at TI0 and at longer TIs while showing decreased precision at TI values below TI0. KEY POINTS: • Synthetic IR imaging retrospectively generates LGE images at any theoretical TI • Synthetic IR imaging can simulate the effect of TI on LGE quantification • Fifteen minutes post-contrast MagIR sy accurately quantifies infarcts from TI 0 to TI 0 + 150 ms • Fifteen minutes post-contrast PSIR sy provides precise infarct size independent of TI • Synthetic IR imaging has further advantages in reducing operator dependence.

Validation of T2* in-line analysis for tissue iron quantification at 1.5 T.

BACKGROUND: There is a need for improved worldwide access to tissue iron quantification using T2* cardiovascular magnetic resonance (CMR). One route to facilitate this would be simple in-line T2* analysis widely available on MR scanners. We therefore compared our clinically validated and established T2* method at Royal Brompton Hospital (RBH T2*) against a novel work-in-progress (WIP) sequence with in-line T2* measurement from Siemens (WIP T2*). METHODS: Healthy volunteers (n = 22) and patients with iron overload (n = 78) were recruited (53 males, median age 34 years). A 1.5 T study (Magnetom Avanto, Siemens) was performed on all subjects. The same mid-ventricular short axis cardiac slice and transaxial slice through the liver were used to acquire both RBH T2* images and WIP T2* maps for each participant. Cardiac white blood (WB) and black blood (BB) sequences were acquired. Intraobserver, interobserver and interstudy reproducibility were measured on the same data from a subset of 20 participants. RESULTS: Liver T2* values ranged from 0.8 to 35.7 ms (median 5.1 ms) and cardiac T2* values from 6.0 to 52.3 ms (median 31 ms). The coefficient of variance (CoV) values for direct comparison of T2* values by RBH and WIP were 6.1-7.8 % across techniques. Accurate delineation of the septum was difficult on some WIP T2* maps due to artefacts. The inability to manually correct for noise by truncation of erroneous later echo times led to some overestimation of T2* using WIP T2* compared with the RBH T2*. Reproducibility CoV results for RBH T2* ranged from 1.5 to 5.7 % which were better than the reproducibility of WIP T2* values of 4.1-16.6 %. CONCLUSIONS: Iron estimation using the T2* CMR sequence in combination with Siemens' in-line data processing is generally satisfactory and may help facilitate global access to tissue iron assessment. The current automated T2* map technique is less good for tissue iron assessment with noisy data at low T2* values.

Automatic Measurement of the Myocardial Interstitium: Synthetic Extracellular Volume Quantification Without Hematocrit Sampling.

OBJECTIVES: The authors sought to generate a synthetic extracellular volume fraction (ECV) from the relationship between hematocrit and longitudinal relaxation rate of blood. BACKGROUND: ECV quantification by cardiac magnetic resonance (CMR) measures diagnostically and prognostically relevant changes in the extracellular space. Current methodologies require blood hematocrit (Hct) measurement-a complication to easy clinical application. We hypothesized that the relationship between Hct and longitudinal relaxation rate of blood (R1 = 1/T1blood) could be calibrated and used to generate a synthetic ECV without Hct that was valid, user-friendly, and prognostic. METHODS: Proof-of-concept: 427 subjects with a wide range of health and disease were divided into derivation (n = 214) and validation (n = 213) cohorts. Histology cohort: 18 patients with severe aortic stenosis with histology obtained during valve replacement. Outcome cohort: For comparison with external outcome data, we applied synthetic ECV to 1,172 consecutive patients (median follow-up 1.7 years; 74 deaths). All underwent CMR scanning at 1.5-T with ECV calculation from pre- and post-contrast T1 (blood and myocardium) and venous Hct. RESULTS: Proof-of-concept: In the derivation cohort, native R1blood and Hct showed a linear relationship (R(2) = 0.51; p < 0.001), which was used to create synthetic Hct and ECV. Synthetic ECV correlated well with conventional ECV (R(2) = 0.97; p < 0.001) without bias. These results were maintained in the validation cohort. Histology cohort: Synthetic and conventional ECV both correlated well with collagen volume fraction measured from histology (R(2) = 0.61 and 0.69, both p < 0.001) with no statistical difference (p = 0.70). Outcome cohort: Synthetic ECV related to all-cause mortality (hazard ratio 1.90; 95% confidence interval 1.55 to 2.31; for every 5% increase in ECV). Finally, we engineered a synthetic ECV tool, generating automatic ECV maps during image acquisition. CONCLUSIONS: Synthetic ECV provides validated noninvasive quantification of the myocardial extracellular space without blood sampling and is associated with cardiovascular outcomes.

Myocardial Late Gadolinium Enhancement: Accuracy of T1 Mapping-based Synthetic Inversion-Recovery Imaging.

PURPOSE: To compare the accuracy of detection and quantification of myocardial late gadolinium enhancement (LGE) with a synthetic inversion-recovery (IR) approach with that of conventional IR techniques. MATERIALS AND METHODS: This prospective study was approved by the institutional review board and compliant with HIPAA. All patients gave written informed consent. Between June and November 2014, 43 patients (25 men; mean age, 54 years ± 16) suspected of having previous myocardial infarction underwent magnetic resonance (MR) imaging, including contrast material-enhanced LGE imaging and T1 mapping. Synthetic magnitude and phase-sensitive IR images were generated on the basis of T1 maps. Images were assessed by two readers. Differences in the per-patient and per-segment LGE detection rates between the synthetic and conventional techniques were analyzed with the McNemar test, and the accuracy of LGE quantification was calculated with the paired t test and Bland-Altman statistics. Interreader agreement for the detection and quantification of LGE was analyzed with κ and Bland-Altman statistics, respectively. RESULTS: Seventeen of the 43 patients (39%) had LGE patterns consistent with myocardial infarction. The sensitivity and specificity of synthetic magnitude and phase-sensitive IR techniques in the detection of LGE were 90% and 95%, respectively, with patient-based analysis and 94% and 99%, respectively, with segment-based analysis. The area of LGE measured with synthetic IR techniques showed excellent agreement with that of conventional techniques (4.35 cm(2) ± 1.88 and 4.14 cm(2)± 1.62 for synthetic magnitude and phase-sensitive IR, respectively, compared with 4.25 cm(2) ± 1.92 and 4.22 cm(2) ± 1.86 for conventional magnitude and phase-sensitive IR, respectively; P > .05). Interreader agreement was excellent for the detection (κ > 0.81) and quantification (bias range, -0.34 to 0.40; P > .05) of LGE. CONCLUSION: The accuracy of the T1 map-based synthetic IR approach in the detection and quantification of myocardial LGE in patients with previous myocardial infarction was similar to that of conventional IR techniques. The use of T1 mapping to derive synthetic LGE images may reduce imaging times and operator dependence in future T1 mapping protocols with full left ventricular coverage.

Saturation pulse design for quantitative myocardial T1 mapping.

BACKGROUND: Quantitative saturation-recovery based T1 mapping sequences are less sensitive to systematic errors than the Modified Look-Locker Inversion recovery (MOLLI) technique but require high performance saturation pulses. We propose to optimize adiabatic and pulse train saturation pulses for quantitative T1 mapping to have <1 % absolute residual longitudinal magnetization (|MZ/M0|) over ranges of B0 and [Formula: see text] (B1 scale factor) inhomogeneity found at 1.5 T and 3 T. METHODS: Design parameters for an adiabatic BIR4-90 pulse were optimized for improved performance within 1.5 T B0 (±120 Hz) and [Formula: see text] (0.7-1.0) ranges. Flip angles in hard pulse trains of 3-6 pulses were optimized for 1.5 T and 3 T, with consideration of T1 values, field inhomogeneities (B0 = ±240 Hz and [Formula: see text]=0.4-1.2 at 3 T), and maximum achievable B1 field strength. Residual MZ/M0 was simulated and measured experimentally for current standard and optimized saturation pulses in phantoms and in-vivo human studies. T1 maps were acquired at 3 T in human subjects and a swine using a SAturation recovery single-SHot Acquisition (SASHA) technique with a standard 90°-90°-90° and an optimized 6-pulse train. RESULTS: Measured residual MZ/M0 in phantoms had excellent agreement with simulations over a wide range of B0 and [Formula: see text]. The optimized BIR4-90 reduced the maximum residual |MZ/M0| to <1 %, a 5.8× reduction compared to a reference BIR4-90. An optimized 3-pulse train achieved a maximum residual |MZ/M0| <1 % for the 1.5 T optimization range compared to 11.3 % for a standard 90°-90°-90° pulse train, while a 6-pulse train met this target for the wider 3 T ranges of B0 and [Formula: see text]. The 6-pulse train demonstrated more uniform saturation across both the myocardium and entire field of view than other saturation pulses in human studies. T1 maps were more spatially homogeneous with 6-pulse train SASHA than the reference 90°-90°-90° SASHA in both human and animal studies. CONCLUSIONS: Adiabatic and pulse train saturation pulses optimized for different constraints found at 1.5 T and 3 T achieved <1 % residual |MZ/M0| in phantom experiments, enabling greater accuracy in quantitative saturation recovery T1 imaging.

White matter integrity of the cerebellar peduncles as a mediator of effects of prenatal alcohol exposure on eyeblink conditioning.

Fetal alcohol spectrum disorders (FASD) are characterized by a range of neurodevelopmental deficits that result from prenatal exposure to alcohol. These can include cognitive, behavioural, and neurological impairment, as well as structural and functional brain damage. Eyeblink conditioning (EBC) is among the most sensitive endpoints affected in FASD. The cerebellar peduncles, large bundles of myelinated nerve fibers that connect the cerebellum to the brainstem, constitute the principal white matter element of the EBC circuit. Diffusion tensor imaging (DTI) is used to assess white matter integrity in fibre pathways linking brain regions. DTI scans of 54 children with FASD and 23 healthy controls, mean age 10.1 ± 1.0 years, from the Cape Town Longitudinal Cohort were processed using voxelwise group comparisons. Prenatal alcohol exposure was related to lower fractional anisotropy (FA) bilaterally in the superior cerebellar peduncles and higher mean diffusivity (MD) in the left middle peduncle, effects that remained significant after controlling for potential confounding variables. Lower FA and higher MD in these regions were associated with poorer EBC performance. Moreover, effects of alcohol exposure on EBC decreased significantly after inclusion of these DTI measures in regression models, suggesting that these white matter deficits partially mediate the relation of prenatal alcohol exposure to EBC. The associations of greater alcohol consumption with these DTI measures are largely attributable to greater radial diffusivity, possibly indicating poorer myelination. Thus, these data suggest that fetal alcohol-related deficits in EBC are attributable, in part, to poorer myelination in key regions of the cerebellar peduncles.