Operator's eye lens dose in computed tomography-guided interventions.

OBJECTIVES: To survey (1) operator's eye lens doses in typical computed tomography (CT)-guided interventions, (2) correlation between dose length product (DLP) and the operator's dose, and (3) different ways for estimating the eye lens dose in clinical settings. METHODS: Doses of 16 radiologists in 164 CT-guided interventional procedures were prospectively measured during a 6-month time period upon radioprotective garments and descriptive statistical outcomes were calculated. The correlations between DLP and measured doses were surveyed. RESULTS: On average, the operator's dose at the eye level (DEL, Hp(0.07)) was 22 µSv per procedure and the personal equivalent dose Hp(10) at the collar level was 21 µSv per procedure. The mean DLP of a procedure was 320 mGy cm, where 54% resulted from the fluoroscopy, the mean exposure time being 18 s. Based on the results, the operator's DEL could be estimated from DLP using the equation DEL (µSv) = 0.10 µSv/mGy cm × patient fluoro DLP (mGycm) (p < 0.001), and the dose at the collar level (DCL) using the equation DCL (µSv) = 0.12 µSv/mGy cm × patient fluoro DLP (mGy cm) (p < 0.001). In addition, DEL (µSv) = 0.7 × DCL (µSv). CONCLUSIONS: The eye lens doses in CT-guided interventions are generally low even without protective equipment, and it is unlikely that the recommended annual equivalent dose limit of 20 mSv for the lens of the eye will be exceeded by conducting CT-guided interventions solely. Eye lens dose can be roughly estimated based on either DLP of the procedure or dose measured at the operator's collar level. KEY POINTS: • Eye lens doses in CT-guided operations are generally low. • It is unlikely that the ICRP recommendation of the yearly equivalent dose limit of 20 mSv will be exceeded by conducting CT-guided interventions solely. • Magnitude of eye lens dose can be estimated based on either DLP of the procedure or dose measured at the operator's collar level.

Quantification of porcine myocardial perfusion with modified dual bolus MRI - a prospective study with a PET reference.

BACKGROUND: The reliable quantification of myocardial blood flow (MBF) with MRI, necessitates the correction of errors in arterial input function (AIF) caused by the T1 saturation effect. The aim of this study was to compare MBF determined by a traditional dual bolus method against a modified dual bolus approach and to evaluate both methods against PET in a porcine model of myocardial ischemia. METHODS: Local myocardial ischemia was induced in five pigs, which were subsequently examined with contrast enhanced MRI (gadoteric acid) and PET (O-15 water). In the determination of MBF, the initial high concentration AIF was corrected using the ratio of low and high contrast AIF areas, normalized according to the corresponding heart rates. MBF was determined from the MRI, during stress and at rest, using the dual bolus and the modified dual bolus methods in 24 segments of the myocardium (total of 240 segments, five pigs in stress and rest). Due to image artifacts and technical problems 53% of the segments had to be rejected from further analyses. These two estimates were later compared against respective rest and stress PET-based MBF measurements. RESULTS: Values of MBF were determined for 112/240 regions. Correlations for MBF between the modified dual bolus method and PET was rs = 0.84, and between the traditional dual bolus method and PET rs = 0.79. The intraclass correlation was very good (ICC = 0.85) between the modified dual bolus method and PET, but poor between the traditional dual bolus method and PET (ICC = 0.07). CONCLUSIONS: The modified dual bolus method showed a better agreement with PET than the traditional dual bolus method. The modified dual bolus method was found to be more reliable than the traditional dual bolus method, especially when there was variation in the heart rate. However, the difference between the MBF values estimated with either of the two MRI-based dual-bolus methods and those estimated with the gold-standard PET method were statistically significant.

Adenoviral intramyocardial VEGF-DΔNΔC gene transfer increases myocardial perfusion reserve in refractory angina patients: a phase I/IIa study with 1-year follow-up.

AIMS: We evaluated for the first time the effects of angiogenic and lymphangiogenic AdVEGF-DΔNΔC gene therapy in patients with refractory angina. METHODS AND RESULTS: Thirty patients were randomized to AdVEGF-DΔNΔC (AdVEGF-D) or placebo (control) groups. Electromechanical NOGA mapping and radiowater PET were used to identify hibernating viable myocardium where treatment was targeted. Safety, severity of symptoms, quality of life, lipoprotein(a) [Lp(a)] and routine clinical chemistry were measured. Myocardial perfusion reserve (MPR) was assessed with radiowater PET at baseline and after 3- and 12-months follow-up. Treatment was well tolerated. Myocardial perfusion reserve increased significantly in the treated area in the AdVEGF-D group compared with baseline (1.00 ± 0.36) at 3 months (1.31 ± 0.46, P = 0.045) and 12 months (1.44 ± 0.48, P = 0.009) whereas MPR in the reference area tended to decrease (2.05 ± 0.69, 1.76 ± 0.62, and 1.87 ± 0.69; baseline, 3 and 12 months, respectively, P = 0.551). Myocardial perfusion reserve in the control group showed no significant change from baseline to 3 and 12 months (1.26 ± 0.37, 1.57 ± 0.55, and 1.48 ± 0.48; respectively, P = 0.690). No major changes were found in clinical chemistry but anti-adenovirus antibodies increased in 54% of the treated patients compared with baseline. AdVEGF-D patients in the highest Lp(a) tertile at baseline showed the best response to therapy (MPR 0.94 ± 0.32 and 1.76 ± 0.41 baseline and 12 months, respectively, P = 0.023). CONCLUSION: AdVEGF-DΔNΔC gene therapy was safe, feasible, and well tolerated. Myocardial perfusion increased at 1 year in the treated areas with impaired MPR at baseline. Plasma Lp(a) may be a potential biomarker to identify patients that may have the greatest benefit with this therapy.

Repaired coarctation of the aorta does not affect four-dimensional flow metrics in bicuspid aortic valve disease.

OBJECTIVES: The objective of this study was primarily to compare four-dimensional flow magnetic resonance imaging metrics in the ascending aorta (AA) of patients with right-left fusion type bicuspid aortic valve (RL-BAV) and repaired coarctation of the aorta (CoA) to RL-BAV without CoA. Metrics of patients with RL-BAV were also compared to the matched group of patients with common tricuspid aortic valve (TAV). METHODS: Eleven patients with RL-BAV and CoA, 11 patients with RL-BAV without CoA and 22 controls with TAV were investigated. Peak velocity (cm/s), peak flow (ml/s) and flow displacement (%) were analysed at 5 pre-defined AA levels. In addition, regional wall shear stress (WSS, mN/m2), circumferential WSS (WSSc) and axial WSS (WSSa) at all levels were quantified in 6 sectors of the aortic circle. Averaged WSS values on each level (WSSavg, WSSc, avg and WSSa, avg) were calculated as well. RESULTS: Peak velocity at the proximal tubular AA was significantly lower in BAV and CoA group (P = 0.047) compared to BAV without CoA. In addition, the WSSa, avg was found to be higher for the BAV and CoA group at proximal AA respectively (P = 0.040). No other significant differences were found between these groups. BAV group's peak velocity was higher at every level (P < 0.001-0.004) compared to TAV group. Flow displacement was significantly higher for the BAV group at every level (P < 0.001) besides at the most distal level. All averaged WSS values were significantly higher in BAV patients in distal AA (P < 0.001-0.018). CONCLUSIONS: Repaired CoA does not relevantly alter four-dimensional flow metrics in the AA of patients with RL-BAV. However, RL-BAV majorly alters flow dynamics in the AA when compared to patients with TAV. CLINICAL TRIAL REGISTRATION NUMBER: https://www.clinicaltrials.gov/study/NCT05065996, Unique Protocol ID 5063566.

4D Flow Versus 2D Phase Contrast MRI in Populations With Bi- and Tricuspid Aortic Valves.

AIM: To compare 4D flow magnetic resonance imaging (MRI) and 2D phase contrast (PC) MRI when evaluating bicuspid (BAV) and tricuspid (TAV) aortic valves. MATERIALS AND METHODS: A total of 83 subjects (35 BAV, 48 TAV) were explored with 4D flow and 2D PC MRI. Systolic peak velocity, peak flow and regurgitation fraction were analysed at two pre-defined aortic levels (aortic root, mid-tubular). Furthermore, the two methods of 4D flow analysis (Heart and Artery) were compared. RESULTS: Correlation between the 2D PC MRI and 4D flow MRI derived parameters ranged from moderate (R=0.58) to high (R=0.90). 4D flow MRI yielded significantly higher peak velocities in the tubular aorta in both groups. Regarding the aortic root, peak velocities were significantly higher in the TAV group with 4D flow MRI, but in the BAV group 4D flow MRI yielded non-significantly lower values. Findings on peak flow differences between the two modalities followed the same pattern as the differences in peak velocities. 4D flow MRI derived regurgitation fraction values were lower in both locations in both groups. Interobserver agreement for different 4D flow MRI acquired parameters varied from poor (ICC=0.07) to excellent (ICC=1.0) in the aortic root, and it was excellent in the tubular aorta (ICC=0.8-1.0). CONCLUSION: 4D flow MRI seems to be accurate in comparison to 2D PC MRI in normal aortic valves and in BAV with mild to moderate stenosis. However, the varying interobserver reproducibility and impaired accuracy at higher flow velocities should be taken into account in clinical practice when using the 4D flow method.

Effect of MOSFET dosimeters' calibration method on calibration factors and radiation doses measured with the dosimeters in radiology.

MOSFET dosimeters have widely been used to measure radiation doses caused by x-rays. When using the MOSFET dosimeters, calibration factors (CFs) have a direct effect on reliability of dose measurements. The aim of this paper was to study the effect of various calibration methods on the CFs of the MOSFET dosimeters. The CFs were measured on clinical digital x-ray angiography (XA) and computed tomography (CT) devices using a calibrated CT ionization chamber and a standard polymethyl methacrylate (PMMA) phantom. The measurements were conducted by having the dosimeters (1) in air, (2) on the surface of the PMMA phantom and (3) inside the phantom. A statistically significant difference was seen between the CFs measured on the XA and CT devices. The CFs measured on the CT device were 20%-165% higher than those measured with the XA device (p < 0.001) in every calibration geometry. Furthermore, the calibration geometry had a notable effect on the CFs on CT. The CFs on the surface of the phantom were 18%-25% higher than in air (p < 0.05), and the CFs inside the phantom were 32%-39% smaller than in air (p < 0.05). These results suggest that the calibration of the MOSFET dosimeters should be conducted with the same device that is used in actual dose measurements. Also, the scattering conditions and the calibration geometry should be similar in the calibration and subsequent dose measurements.

Cardiac MRI assessed left ventricular hypertrophy in differentiating hypertensive heart disease from hypertrophic cardiomyopathy attributable to a sarcomeric gene mutation.

OBJECTIVE: To evaluate the value of cardiac magnetic resonance imaging (CMRI)-assessed left ventricular hypertrophy (LVH) in differentiating between hypertensive heart disease and hypertrophic cardiomyopathy (HCM). METHODS: 95 unselected subjects with mild-to-moderate hypertension, 24 patients with HCM attributable to the D175N mutation of the α-tropomyosin gene and 17 control subjects were studied by cine CMRI. Left ventricular (LV) quantitative and qualitative characteristics were evaluated. RESULTS: LV maximal end-diastolic wall thickness, wall thickness-to-LV volume ratio, end-diastolic septum thickness and septum-to-lateral wall thickness ratio were useful measures for differentiating between LVH due to hypertension and HCM. The most accurate measure for identifying patients with HCM was the LV maximal wall thickness ≥ 17 mm, with a sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 90%, 93%, 86%, 95% and 91%, respectively. LV maximal wall thickness in the anterior wall, or regional bulging in left ventricular wall was found only in patients with HCM. LV mass index was not discriminant between patients with HCM and those with LVH due to hypertension. CONCLUSION: LV maximal thickness measured by CMRI is the best anatomical parameter in differentiating between LVH due to mild-to-moderate hypertension and HCM attributable to a sarcomeric mutation. CMRI assessment of location and quality of LVH is also of value in differential diagnosis.

Quantification of Myocardial Blood Flow by Machine Learning Analysis of Modified Dual Bolus MRI Examination.

Contrast-enhanced magnetic resonance imaging (MRI) is a promising method for estimating myocardial blood flow (MBF). However, it is often affected by noise from imaging artefacts, such as dark rim artefact obscuring relevant features. Machine learning enables extracting important features from such noisy data and is increasingly applied in areas where traditional approaches are limited. In this study, we investigate the capacity of machine learning, particularly support vector machines (SVM) and random forests (RF), for estimating MBF from tissue impulse response signal in an animal model. Domestic pigs (n = 5) were subjected to contrast enhanced first pass MRI (MRI-FP) and the impulse response at different regions of the myocardium (n = 24/pig) were evaluated at rest (n = 120) and stress (n = 96). Reference MBF was then measured using positron emission tomography (PET). Since the impulse response may include artefacts, classification models based on SVM and RF were developed to discriminate noisy signal. In addition, regression models based on SVM, RF and linear regression (for comparison) were developed for estimating MBF from the impulse response at rest and stress. The classification and regression models were trained on data from 4 pigs (n = 168) and tested on 1 pig (n = 48). Models based on SVM and RF outperformed linear regression, with higher correlation (R SVM 2 = 0.81, R RF 2 = 0.74, R linear_regression 2 = 0.60; ρSVM = 0.76, ρRF = 0.76, ρlinear_regression = 0.71) and lower error (RMSESVM = 0.67 mL/g/min, RMSERF = 0.77 mL/g/min, RMSElinear_regression = 0.96 mL/g/min) for predicting MBF from MRI impulse response signal. Classifier based on SVM was optimal for detecting impulse response signals with artefacts (accuracy = 92%). Modified dual bolus MRI signal, combined with machine learning, has potential for accurately estimating MBF at rest and stress states, even from signals with dark rim artefacts. This could provide a protocol for reliable and easy estimation of MBF, although further research is needed to clinically validate the approach.

Preinterventional quantitative magnetic resonance imaging predicts uterus and leiomyoma size reduction after uterine artery embolization.

PURPOSE: To investigate the relationship between magnetic resonance imaging (MRI) measures and uterus and leiomyoma size reductions after uterine artery embolization (UAE). MATERIALS AND METHODS: Fifty-two women with leiomyomas underwent selective UAEs. Uterine and dominant leiomyoma sizes were measured with preinterventional MRI and a 6-month follow-up MRI. Four MRI measures of the dominant leiomyoma were recorded: T1 time; T2 time; leiomyoma-to-skeletal muscle T2 SI-ratio; and percentage of contrast enhancement. To evaluate the predictive value of MRI measures we used Spearman rank correlation, area under the receiver operating characteristic (ROC) curve (A(z)), and values for diagnostic performance. RESULTS: Uterus and dominant leiomyoma size reductions were highly variable. Leiomyoma size reductions of >or=75% were accurately predicted with leiomyoma-to-skeletal muscle T2 SI-ratio (ROC curve A(z) = 0.930; 95% confidence interval [CI]: 0.853, 1.000). Leiomyoma size reductions >or=75% were predicted by leiomyoma-to-skeletal muscle T2 SI-ratio >or=3.5 and T1-time >or=750 msec with 100% and 86% sensitivities and 67% and 72% specificities, respectively. Uterus size reduction >or=50% were identified by dominant leiomyoma-to-skeletal muscle T2 SI-ratio >or=2.5. CONCLUSION: Uterus and dominant leiomyoma size reductions after UAE were predicted with preoperative MRI measures of the dominant leiomyoma.

Extrapyramidal side-effects and dopamine D(2/3) receptor binding in substantia nigra.

BACKGROUND: The exact mechanisms for antipsychotic-induced extrapyramidal side-effects have remained obscure despite intensive research. Previous studies have highlighted a central role for nigral dopamine D(2) receptors in the control of motor functions. AIMS: The aim of the present study was to examine relationships between dopamine D(2) receptor binding in both substantia nigra and temporal cortex with extrapyramidal symptoms among antipsychotic-treated patients with schizophrenia. METHODS: Single-photon emission-computed tomography (SPECT) ligand [(123)I]epidepride was used to determine dopamine D(2/3) apparent binding potential in 13 antipsychotic-treated (seven with clozapine, four with olanzapine and two with haloperidol) patients with schizophrenia. Extrapyramidal symptoms were assessed with the Simpson and Angus Scale (SAS). RESULTS: A statistically significant correlation was observed between dopamine D(2/3) receptor apparent binding potential in the substantia nigra and extrapyramidal side-effects (r = -0.62, P = 0.024). No correlations were detected in the temporal cortex between dopamine D(2/3) receptor binding and extrapyramidal side-effects. CONCLUSIONS: These findings support the role of dopamine D(2) autoreceptors in substantia nigra regarding drug-induced movement disorders.

CONTEMPORARY RADIATION DOSES IN INTERVENTIONAL CARDIOLOGY: A NATIONWIDE STUDY OF PATIENT SKIN DOSES IN FINLAND.

In contemporary interventional cardiology, for typical elderly patients, the most severe radiation-related harm to patients can be considered to come from skin exposures. In this paper, maximum local skin doses in cardiological procedures are explored with Gafchromic film dosimetry. Film and reader calibrations and reading were performed at the Secondary Standards Dosimetry Laboratory of the Radiation and Nuclear Safety Authority (STUK), and data were gathered from seven hospitals in Finland. As alert levels for early transient erythema, 200 Gycm2 kerma area product (KAP) and 2000 mGy air kerma levels for transcatheter aortic valve implantations (TAVI) procedures are proposed. The largest doses were measured in TAVI (4158.8 mGy) and percutaneous coronary interventions (PCI) (941.68 mGy). Accuracies of the GE DoseWatch and Siemens CareMonitor skin dose estimates were reasonable, but more results are needed to reliably assess and validate the tools' capabilities and reliabilities. Uncertainty of the Gafchromic dosimetry was estimated as 9.1% for a calibration with seven data points and 19.3% for a calibration with five data points.

Dopamine D2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine.

AIMS: Aberrant dopamine transmission in extrastriatal brain regions has been repeatedly illustrated among patients with schizophrenia. Differences between typical and second-generation antipsychotics in dopamine D(2) receptor modulation within various brain areas remain a topic for debate. The aim of the present study was therefore to investigate dopamine D(2/3) receptor apparent binding potential (BP(app)) and occupancy in midbrain and temporal cortex among clozapine-, olanzapine- and haloperidol-treated schizophrenia patients. METHODS: Dopamine D(2/3) binding was studied on single-photon emission computed tomography ligand [(123)I]epidepride in 13 schizophrenia patients treated with medication (two with haloperidol, four with olanzapine and seven with clozapine), six drug-naïve patients and seven healthy controls. RESULTS: Statistically significant differences in midbrain dopamine D(2/3) receptor BP(app) (P = 0.015) and occupancy (P = 0.016) were observed between the clozapine, olanzapine and haloperidol groups. The lowest occupancy was found in clozapine-treated patients (5%), followed by olanzapine-treated patients (28%), compared to haloperidol-treated patients (40%). No significant differences were observed in the temporal poles. Occupancy changed substantially depending on the comparison group used (either drug-naïve vs healthy controls) in the examined brain areas (P = 0.001), showing an overestimation with all antipsychotics when the healthy control group was used. CONCLUSION: Both typical and second-generation antipsychotics occupy cortical dopamine D(2/3) receptors, thus mediating therapeutic efficacy. Observed differences in midbrain dopamine D(2/3) occupancy between classical antipsychotics and second-generation antipsychotics may have clinical relevance by modulating altered nigrostriatal dopamine neurotransmission during the acute phase of schizophrenia.

Using the Disease State Fingerprint Tool for Differential Diagnosis of Frontotemporal Dementia and Alzheimer's Disease.

BACKGROUND: Disease State Index (DSI) and its visualization, Disease State Fingerprint (DSF), form a computer-assisted clinical decision making tool that combines patient data and compares them with cases with known outcomes. AIMS: To investigate the ability of the DSI to diagnose frontotemporal dementia (FTD) and Alzheimer's disease (AD). METHODS: The study cohort consisted of 38 patients with FTD, 57 with AD and 22 controls. Autopsy verification of FTD with TDP-43 positive pathology was available for 14 and AD pathology for 12 cases. We utilized data from neuropsychological tests, volumetric magnetic resonance imaging, single-photon emission tomography, cerebrospinal fluid biomarkers and the APOE genotype. The DSI classification results were calculated with a combination of leave-one-out cross-validation and bootstrapping. A DSF visualization of a FTD patient is presented as an example. RESULTS: The DSI distinguishes controls from FTD (area under the receiver-operator curve, AUC = 0.99) and AD (AUC = 1.00) very well and achieves a good differential diagnosis between AD and FTD (AUC = 0.89). In subsamples of autopsy-confirmed cases (AUC = 0.97) and clinically diagnosed cases (AUC = 0.94), differential diagnosis of AD and FTD performs very well. CONCLUSIONS: DSI is a promising computer-assisted biomarker approach for aiding in the diagnostic process of dementing diseases. Here, DSI separates controls from dementia and differentiates between AD and FTD.

Electrocardiographic left ventricular hypertrophy has low diagnostic accuracy in middle-aged subjects.

OBJECTIVE: To evaluate the usefulness of electrocardiographic left ventricular hypertrophy (ECG LVH) as a marker of LVH in middle-aged subjects. METHODS: LVH was determined by cardiovascular magnetic resonance imaging (MRI) in 188 apparently healthy middle-aged [97 men (45+/-7 years) and 91 women (47+/-6 years)]. Receiver operating characteristic (ROC) curves, test sensitivity, specificity, positive and negative predictive values for identifying LVH at different ECG criteria were calculated. RESULTS: Systolic and diastolic blood pressures were 142+/-13 mmHg and 90+/-8 mmHg in men and 139+/-10 mmHg and 90+/-8 mmHg in women, respectively. LVMI was 78+/-17 g/m2 in men and 67+/-12 g/m2 in women, and 14% of men and 22% of women had LVH in cardiac MRI. Only Sokolow-Lyon and Sokolow-Lyon product had the area under the ROC curve over 0.70. Sokolow-Lyon product had the highest sensitivity (47%). All ECG criteria had high negative predictive values, but the positive predictive values were below 46%. CONCLUSIONS: Commonly used ECG criteria of LVH have low discrimination ability in middle-aged subjects. ECG LVH alone should not be used as a marker of target organ damage in middle-aged, never treated and apparently healthy hypertensives.

Midbrain dopamine D2/3 receptor binding in schizophrenia.

Several studies suggest that dysregulation of dopaminergic transmission in the midbrain and thalamus may contribute to the symptomatology of schizophrenia. The objective of this study was to examine the putative alteration of dopamine D(2/3 )receptor densities in the thalamus and midbrain of drug-naïve schizophrenic patients. We used the high-affinity single-photon emission tomography ligand [(123)I]epidepride for imaging D(2/3 )receptor binding sites in six neuroleptic-naïve schizophrenic patients, and seven healthy controls. Schizophrenic symptoms were evaluated by the Positive and Negative Syndrome Scale. Significantly lower D(2/3 )values were observed in the midbrain of patients with schizophrenia compared to controls (P = 0.02). No statistically significant difference was observed in the thalamus between two groups. Negative correlations were found between thalamic D(2/3 )receptor binding and general psychopathological schizophrenic symptoms (r from -0.78 to -0.92). These observations implicate altered dopaminergic activity in the midbrain of schizophrenic patients.