Pharmacological therapies for male infertility.

Male factor infertility is a multifaceted problem that affects approximately 50% of couples suffering from infertility. Causes of male infertility include endocrine disturbances, gonadotoxins, genetic abnormalities, varicocele, malignancies, infections, congenital or acquired urogenital abnormalities, iatrogenic factors, immunological factors, and idiopathic reasons. There are a variety of treatment options for male infertility, depending on the underlying cause(s). These can include surgical treatments, medical/hormonal therapies, and assisted reproductive techniques (ART), which can be combined with surgical sperm retrieval (SSR) if necessary. In this review article, the pharmacological therapies for male infertility are grouped by their underlying causes. Some of these therapies are targeted and specific, while others are used empirically to treat idiopathic male infertility. This will include treatments to optimize infertility in patients who have hypogonadism, ejaculatory dysfunction, infections, or idiopathic male infertility. Finally, we will provide an overview of the future directions of pharmacological therapies for male infertility. Significance Statement Male infertility is a significant worldwide problem. Detailed knowledge of the pharmacological therapies available will ensure the prescription of appropriate therapy and avoid the use of unnecessary or harmful treatments.

Differentiation between nonobstructive azoospermia and obstructive azoospermia: then and now.

Male infertility has seen an increase in prevalence with cases of azoospermia estimated to affect 10%-15% of infertile men. Confirmation of azoospermia subsequently necessitates an early causal differentiation between obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). Although less common when compared to NOA, OA can represent upward 20%-40% of cases of azoospermia. While there are a multitude of etiologies responsible for causing NOA and OA, correctly distinguishing between the two types of azoospermia has profound implications in managing the infertile male. This review represents an amalgamation of the current guidelines and literature which will supply the reproductive physician with a diagnostic armamentarium to properly distinguish between NOA and OA, therefore providing the best possible care to the infertile couple.

Nonobstructive azoospermia: an etiologic review.

ABSTRACT: Azoospermia is the complete absence of spermatozoa in the ejaculate in two or more semen analyses after centrifugation. Nonobstructive azoospermia (NOA) represents the most severe form of male factor infertility accounting for 10%-15% of cases and stems from an impairment to spermatogenesis. Understanding of the hypothalamic-pituitary-testicular axis has allowed NOA to be subcategorized by anatomic and/or pathophysiologic level. The etiologies of NOA, and therefore, the differential diagnoses when considering NOA as a cause of male factor infertility, can be subcategorized and condensed into several distinct classifications. Etiologies of NOA include primary hypogonadism, secondary hypogonadism, defects in androgen synthesis and/or response, defective spermatogenesis and sperm maturation, or a mixed picture thereof. This review includes up-to-date clinical, diagnostic, cellular, and histologic features pertaining to the multitude of NOA etiologies. This in turn will provide a framework by which physicians practicing infertility can augment their clinical decision-making, patient counseling, thereby improving upon the management of men with NOA.

Reproducibility of a single-volume dynamic CT myocardial blood flow measurement technique: validation in a swine model.

BACKGROUND: We prospectively assessed the reproducibility of a novel low-dose single-volume dynamic computed tomography (CT) myocardial blood flow measurement technique. METHODS: Thirty-four pairs of measurements were made under rest and stress conditions in 13 swine (54.3 ± 12.3 kg). One or two acquisition pairs were acquired in each animal with a 10-min delay between each pair. Contrast (370 mgI/mL; 0.5 mL/kg) and a diluted contrast/saline chaser (0.5 mL/kg; 30:70 contrast/saline) were injected peripherally at 5 mL/s, followed by bolus tracking and acquisition of a single volume scan (100 kVp; 200 mA) with a 320-slice CT scanner. Bolus tracking and single volume scan data were used to derive perfusion in mL/min/g using a first-pass analysis model; the coronary perfusion territories of the left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA) were automatically assigned using a previously validated minimum-cost path technique. The reproducibility of CT myocardial perfusion measurement within the LAD, LCx, RCA, and the whole myocardium was assessed via regression analysis. The average CT dose index (CTDI) of perfusion measurement was recorded. RESULTS: The repeated first (Pmyo1) and second (Pmyo2) single-volume CT perfusion measurements were related by Pmyo2 = 1.01Pmyo1 - 0.03(ρ = 0.96; RMSE = 0.08 mL/min/g; RMSE = 0.07 mL/min/g) for the whole myocardium, and by Preg2 = 0.86Preg1 + 0.13(ρ = 0.87; RMSE = 0.31 mL/min/g; RMSE = 0.29 mL/min/g) for the LAD, LCx, and RCA perfusion territories. The average CTDI of the single-volume CT perfusion measurement was 10.5 mGy. CONCLUSION: The single-volume CT blood flow measurement technique provides reproducible low-dose myocardial perfusion measurement using only bolus tracking data and a single whole-heart volume scan. RELEVANCE STATEMENT: The single-volume CT blood flow measurement technique is a noninvasive tool that reproducibly measures myocardial perfusion and provides coronary CT angiograms, allowing for simultaneous anatomic-physiologic assessment of myocardial ischemia. KEY POINTS: A low-dose single-volume dynamic CT myocardial blood flow measurement technique is reproducible. Motion misregistration artifacts are eliminated using a single-volume CT perfusion technique. This technique enables combined anatomic-physiologic assessment of coronary artery disease.

Low-dose quantitative CT myocardial flow measurement using a single volume scan: phantom and animal validation.

Purpose: To validate a low-dose, single-volume quantitative CT myocardial flow technique in a cardiovascular flow phantom and a swine animal model of coronary artery disease. Approach: A cardiovascular flow phantom was imaged dynamically over different flow rates (0.97 to 2.45 mL/min/g) using 15 mL of contrast per injection. Six swine (37±8 kg) were also imaged dynamically, with different left anterior descending coronary artery balloon stenoses assessed under intracoronary adenosine stress, using 1 mL/kg of contrast per injection. The resulting images were used to simulate dynamic bolus tracking and peak volume scan acquisition. After which, first-pass single-compartment modeling was performed to derive quantitative flow, where the pre-contrast myocardial attenuation was assumed to be spatially uniform. The accuracy of CT flow was then assessed versus ultrasound and microsphere flow in the phantom and animal models, respectively, using regression analysis. Results: Single-volume quantitative CT flow measurements in the phantom (QCT_PHANTOM) were related to reference ultrasound flow measurements (QUS) by QCT_PHANTOM=1.04 QUS-0.1 (Pearson's r=0.98; RMSE=0.09 mL/min/g). In the animal model (QCT_ANIMAL), they were related to reference microsphere flow measurements (QMICRO) by QCT_ANIMAL=1.00 QMICRO-0.05 (Pearson's r=0.96; RMSE=0.48 mL/min/g). The effective dose per CT measurement was 1.21 mSv. Conclusions: The single-volume quantitative CT flow technique only requires bolus tracking data, spatially uniform pre-contrast myocardial attenuation, and a single volume scan acquired near the peak aortic enhancement for accurate, low-dose, myocardial flow measurement (in mL/min/g) under rest and adenosine stress conditions.

Validation of an automated technique for quantification of pulmonary perfusion territories using computed tomography angiography.

Background: Computed tomography pulmonary angiography (CTPA) is the primary modality for the detection and diagnosis of pulmonary embolism (PE) while the stratification of PE severity remains challenging using angiography. Hence, an automated minimum-cost path (MCP) technique was validated to quantify the subtended lung tissue distal to emboli using CTPA. Methods: A Swan-Ganz catheter was placed in the pulmonary artery of seven swine (body weight: 42.6±9.6 kg) to produce different PE severities. A total of 33 embolic conditions were generated, where the PE location was adjusted under fluoroscopic guidance. Each PE was induced by balloon inflation followed by computed tomography (CT) pulmonary angiography and dynamic CT perfusion scans using a 320-slice CT scanner. Following image acquisition, the CTPA and the MCP technique were used to automatically assign the ischemic perfusion territory distal to the balloon. Dynamic CT perfusion was used as the reference standard (REF) where the low perfusion territory was designated as the ischemic territory. The accuracy of the MCP technique was then evaluated by quantitatively comparing the MCP-derived distal territories to the perfusion-derived reference distal territories by mass correspondence using linear regression, Bland-Altman analysis, and paired sample t-test. The spatial correspondence was also assessed. Results: The MCP-derived distal territory masses (MassMCP, g) and the reference standard ischemic territory masses (MassREF, g) were related by MassMCP=1.02MassREF - 0.62 g (r=0.99, paired t-test P=0.51). The mean Dice similarity coefficient was 0.84±0.08. Conclusions: The MCP technique enables accurate assessment of lung tissue at risk distal to a PE using CTPA. This technique can potentially be used to quantify the fraction of lung tissue at risk distal to PE to further improve the risk stratification of PE.

Contrast media timing optimization for coronary CT angiography: a retrospective validation study in swine.

OBJECTIVES: The objective was to retrospectively develop a protocol in swine for optimal contrast media timing in coronary CT angiography (CCTA). METHODS: Several dynamic acquisitions were performed in 28 swine (55 ± 24 kg) with cardiac outputs between 1.5 and 5.5 L/min, for 80 total acquisitions. The contrast was injected (1mL/kg, 5mL/s, Isovue 370), followed by dynamic scanning of the entire aortic enhancement curve, from which the true peak time and aortic and coronary enhancements were recorded as the reference standard. Each dataset was then used to simulate two different CCTA protocols-a new optimal protocol and a standard clinical protocol. For the optimal protocol, the CCTA was acquired after bolus tracking-based trigging using a variable time delay of one-half the contrast injection time interval plus 1.5 s. For the standard protocol, the CCTA was acquired after bolus tracking-based triggering using a fixed time delay of 5 s. For both protocols, the CCTA time, aortic enhancement, coronary enhancement, and coronary contrast-to-noise ratio (CNR) were quantitatively compared to the reference standard measurements. RESULTS: For the optimal protocol, the angiogram was acquired within -0.15 ± 0.75 s of the true peak time, for a mean coronary CNR within 7% of the peak coronary CNR. Conversely, for the standard CCTA protocol, the angiogram was acquired within -1.82 ± 1.71 s of the true peak time, for a mean coronary CNR that was 23% lower than the peak coronary CNR. CONCLUSIONS: The optimal CCTA protocol improves contrast media timing and coronary CNR by acquiring the angiogram at the true aortic root peak time. KEY POINTS: • This study in swine retrospectively developed the mathematical basis of an improved approach for optimal contrast media timing in CCTA. • By combining dynamic bolus tracking with a simple contrast injection timing relation, CCTA can be acquired at the peak of the aortic root enhancement. • CCTA acquisition at the peak of the aortic root enhancement should maximize the coronary enhancement and CNR, potentially improving the accuracy of CT-based assessment of coronary artery disease.

A patient-specific timing protocol for improved CT pulmonary angiography.

Rationale and objectives: To improve the image quality of CT pulmonary angiography (CTPA) using a patient-specific timing protocol. Material and methods: A total of 24 swine (48.5 ± 14.3 kg) underwent continuous contrast-enhanced dynamic CT acquisition over 30 s to capture the pulmonary arterial input function (AIF). Multiple contrast injections were made under different cardiac outputs (1.4-5.1 L/min), resulting in a total of 154 AIF curves. The volume scans with maximal enhancement in these AIF curves were retrospectively selected as the reference standard (group A). Two prospective CTPA protocols with bolus-tracking were then simulated using these AIF curves: one used a fixed delay of 5 s between triggering and CTPA acquisition (group B), while the other used a specific delay based on one-half of the contrast injection duration (group C). The mean attenuation, signal-to-noise (SNR) and contrast-to-noise ratios (CNR) between the three groups were then compared using independent sample t-test. Subjective image quality scores were also compared using Wilcoxon-Mann-Whitney test. Results: The mean attenuation of pulmonary arteries for group A, B and C (expressed in [HU]) were 870.1 ± 242.5 HU, 761.1 ± 246.7 HU and 825.2 ± 236.8 HU, respectively. The differences in the mean SNR and CNR between Group A and Group C were not significant (SNR: 65.2 vs. 62.4, CNR: 59.6 vs. 56.4, both p > 0.05), while Group B was significantly lower than Group A (p < 0.05). Conclusion: The image quality of CT pulmonary angiography is significantly improved with a timing protocol determined using contrast injection delivery time, as compared with a standard timing protocol with a fixed delay between bolus triggering and image acquisition.

White Matter Integrity in Men With Benign Prostatic Hyperplasia and Bladder Outlet Obstruction and Its Contribution to Lower Urinary Tract Symptoms.

PURPOSE: Lower urinary tract symptoms (LUTS) associated with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) can negatively impact quality of life. We evaluated the structural connectivity of the brain in men with BPH with chronic BOO using diffusion tensor imaging (DTI). METHODS: Ambulatory male patients aged ≥45 years with BPH and BOO were recruited. LUTS was defined as an International Prostate Symptom Score (IPSS) ≥12 and a maximum urinary flow rate ≤15 mL/sec. Upon recruitment, uroflowmetry and validated questionnaires regarding bladder status were collected. DTI images from each subject were aligned with the ICBM-DTI-81 atlas, defining 50 white matter tracts (WMTs). The mean values of DTI parameters-fractional anisotropy and mean diffusivity-for each WMT were extracted. These measures were then utilized to compute Pearson correlation coefficients with clinical parameters. Objective clinical parameters included uroflowmetry parameters, postvoid residual (PVR) volume, and bladder capacity. Subjective clinical parameters were assessed using validated questionnaires: the IPSS, Incontinence Symptom Index, and Sexual Health Inventory for Men. RESULTS: The correlation analysis revealed 15 WMTs that showed statistically significant associations (P<0.05) with objective and subjective clinical parameters. Eight tracts were associated with uroflowmetry parameters: maximum flow rate (Qmax), mean flow rate (Qmean), and PVR. Among these tracts, the middle cerebellar peduncles and left medial lemniscus were associated with Qmax; the genu of the corpus callosum, left superior corona radiata, corticospinal tract, right medial lemniscus, posterior corona radiata with Qmean; and the left posterior corona radiata with PVR. Seven tracts also demonstrated significant associations with the IPSS. CONCLUSION: Our results suggest correlations between the preserved white matter integrity of specific WMTs and the severity of LUTS based on objective and subjective clinical parameters, leading us to believe that a distinct pathology of the central nervous system might exist.

Dynamic CT myocardial perfusion without image registration.

The aim of this study was to validate a motion-immune (MI) solution to dynamic CT myocardial perfusion measurement, in the presence of motion without image registration. The MI perfusion technique was retrospectively validated in six swine (37.3 ± 7.5 kg) with a motion-susceptible (MS) perfusion technique performed for comparison. In each swine, varying severities of stenoses were generated in the left anterior descending (LAD) coronary artery using a balloon under intracoronary adenosine stress, followed by contrast-enhanced imaging with 20 consecutive volume scans per stenosis. Two volume scans were then systematically selected from each acquisition for both MI and MS perfusion measurement, where the resulting LAD and left circumflex (LCx) measurements were compared to reference microsphere perfusion measurements using regression and diagnostic performance analysis. The MI (PMI) and microsphere (PMICRO) perfusion measurements were related through regression by PMI = 0.98 PMICRO + 0.03 (r = 0.97), while the MS (PMS) and microsphere (PMICRO) perfusion measurements were related by PMS = 0.62 PMICRO + 0.15 (r = 0.89). The accuracy of the MI and MS techniques in detecting functionally significant stenosis was 93% and 84%, respectively. The motion-immune (MI) perfusion technique provides accurate myocardial perfusion measurement in the presence of motion without image registration.

Supraspinal Neural Changes in Men With Benign Prostatic Hyperplasia Undergoing Bladder Outlet Procedures: A Pilot Functional MRI Study.

OBJECTIVE: To explore brain activation patterns on functional MRI (fMRI) in men with BPH and BOO before and after outlet obstruction procedures. METHODS: Men age ≥45 who failed conservative BPH therapy planning to undergo BOO procedures were recruited. Eligible men underwent a concurrent fMRI/urodynamics testing before and 6 months after BOO procedure. fMRI images were obtained via 3 Tesla MRI. Significant blood-oxygen-level-dependent (BOLD) signal activated voxels (P <.05) were identified at strong desire to void and (attempt at) voiding initiation pre- and post-BOO procedure. RESULTS: Eleven men were enrolled, of which 7 men completed the baseline scan, and 4 men completed the 6-month follow-up scan. Baseline decreased BOLD activity was observed in right inferior frontal gyrus (IFG), bilateral insula, inferior frontal gyrus (IFG) and thalamus. Significant changes in BOLD signal activity following BOO procedures were observed in the insula, IFG, and cingulate cortices. CONCLUSIONS: This represents a pilot study evaluating cortical activity in men with BPH and BOO. Despite limitations we found important changes in supraspinal activity in men with BPH and BOO during filling and emptying phases at baseline and following BOO procedure, with the potential to improve our understanding of neuroplasticity secondary to BPH and BOO. This preliminary data may serve as the foundation for larger future trials.

Contrast timing optimization of a two-volume dynamic CT pulmonary perfusion technique.

The purpose of this study is to develop and validate an optimal timing protocol for a low-radiation-dose CT pulmonary perfusion technique using only two volume scans. A total of 24 swine (48.5 ± 14.3 kg) underwent contrast-enhanced dynamic CT. Multiple contrast injections were made under different pulmonary perfusion conditions, resulting in a total of 141 complete pulmonary arterial input functions (AIFs). Using all the AIF curves, an optimal contrast timing protocol was developed for a first-pass, two-volume dynamic CT perfusion technique (one at the base and the other at the peak of AIF curve). A subset of swine was used to validate the prospective two-volume pulmonary perfusion technique. The prospective two-volume perfusion measurements were quantitatively compared to the previously validated retrospective perfusion measurements with t-test, linear regression, and Bland-Altman analysis. As a result, the pulmonary artery time-to-peak ([Formula: see text]) was related to one-half of the contrast injection duration ([Formula: see text]) by [Formula: see text] (r = 0.95). The prospective two-volume perfusion measurements (PPRO) were related to the retrospective measurements (PRETRO) by PPRO = 0.87PRETRO + 0.56 (r = 0.88). The CT dose index and size-specific dose estimate of the two-volume CT technique were estimated to be 28.4 and 47.0 mGy, respectively. The optimal timing protocol can enable an accurate, low-radiation-dose two-volume dynamic CT perfusion technique.

Preliminary Analysis of Brain Footprints in Multiple Sclerosis Females With Detrusor Sphincter Dyssynergia: A Concurrent Urodynamic and Functional Magnetic Resonance Imaging Study.

PURPOSE: This study evaluates the grey and white brain matter characteristics in women with multiple sclerosis (MS) and detrusor sphincter dyssynergia (DSD). Grey matter is assessed via the functional connectivity (FC) of brain regions activated during voiding, using functional magnetic resonance imaging (fMRI). Two white matter tracts involved in bladder function, the anterior thalamic radiation (ATR) and superior longitudinal fasciculus (SLF), were evaluated using diffusion tensor imaging. METHODS: Twenty-seven women with MS (2 groups: no-DSD [n=23] or DSD [n=4]), and 8 healthy controls (HCs) underwent concurrent urodynamic-fMRI evaluation with 4 cycles of bladder filling and emptying. A FC similarity measure (FC_sim) was calculated for each subject to express the similarity of individual FC at voiding initiation compared to all FC patterns. ATR and SLF tracts were traced and their fractional anisotropy (FA) and mean diffusivity (MD) were recorded. RESULTS: Mean FC_sim values were significantly different among the 3 groups indicating distinct FC patterns; however, no significant difference was found between DSD and no-DSD groups. DSD group showed trends of lower FA and higher MD- indicating loss of coherence-in all tracts compared to HCs, and in the left and right ATR when compared to MS women with neither DSD nor voiding dysfunction (VD), suggesting more damage in these tracts for MS women with DSD. CONCLUSION: Women with MS show distinctly different FC patterns compared to HCs. There are trends showing more damage in the ATR in women with MS and DSD compared to those with neither DSD nor VD.

Absolute cerebral blood flow: Assessment with a novel low-radiation-dose dynamic CT perfusion technique in a swine model.

RATIONALE AND OBJECTIVES: To validate the accuracy of a novel low-dose dynamic CT perfusion technique in a swine model using fluorescent microsphere measurement as the reference standard. MATERIALS AND METHODS: Contrast-enhanced dynamic CT perfusion was performed in five swine at baseline and following brain embolization. Reference microspheres and intravenous contrast (370 mg/ml iodine, 1 ml/kg) were injected (5 ml/s), followed by dynamic CT perfusion. Scan parameters were 320×0.5 mm, 100 kVp and 200 mA. On average, 47 contrast-enhanced volume scans were acquired per acquisition to capture the time attenuation curve. For each acquisition, only two systematically selected volume scans were used to quantify brain perfusion with first-pass analysis technique. The first volume scan was selected at the base, simulating bolus tracking, while the second volume at the peak of the time attenuation curve similar to a CT angiogram. Regional low-dose CT perfusion measurements were compared to the microsphere perfusion measurements with t-test, linear regression and Bland-Altman analysis. The radiation dose of the two-volume CT perfusion technique was determined. RESULTS: Low-dose CT perfusion measurements (PCT) showed excellent correlation with reference microsphere perfusion measurements (PMICRO) by PCT = 1.15 PMICRO - 0.01 (r = 0.93, p ≤ 0.01). The CT dose index and dose-length product for the two-volume CT perfusion technique were 25.6 mGy and 409.6 mGy, respectively. CONCLUSIONS: The accuracy and repeatability of a low-dose dynamic CT perfusion technique was validated in a swine model. This technique has the potential for accurate diagnosis and follow up of stroke and vasospasm.

Combining perfusion and angiography with a low-dose cardiac CT technique: a preliminary investigation in a swine model.

Morphological and physiological assessment of coronary artery disease (CAD) is necessary for proper stratification of CAD risk. The objective was to evaluate a low-dose cardiac CT technique that combines morphological and physiological assessment of CAD. The low-dose technique was evaluated in twelve swine, where three of the twelve had coronary balloon stenosis. The technique consisted of rest perfusion measurement combined with angiography followed by stress perfusion measurement, where the ratio of stress to rest was used to derive coronary flow reserve (CFR). The technique only required two volume scans for perfusion measurement in mL/min/g; hence, four volume scans were acquired in total; two for rest with angiography and two for stress. All rest, stress, and CFR measurements were compared to a previously validated reference technique that employed 20 consecutive volume scans for rest perfusion measurement combined with angiography, and stress perfusion measurement, respectively. The 32 cm diameter volumetric CT dose index ([Formula: see text]) and size-specific dose estimate (SSDE) of the low-dose technique were also recorded. All low-dose perfusion measurements (PLOW) in mL/min/g were related to reference perfusion measurements (PREF) through regression by PLOW = 1.04 PREF - 0.08 (r = 0.94, RMSE = 0.32 mL/min/g). The [Formula: see text] and SSDE of the low-dose cardiac CT technique were 8.05 mGy and 12.80 mGy respectively, corresponding to an estimated effective dose and size-specific effective dose of 1.8 and 2.87 mSv, respectively. Combined morphological and physiological assessment of coronary artery disease is feasible using a low-dose cardiac CT technique.

Long term outcomes of ureteroscopic management of upper tract urothelial carcinoma.

OBJECTIVES: Upper tract urothelial carcinoma (UTUC) is relatively rare. While nephroureterectomy is considered the gold standard for treatment, endoscopic nephron- sparing techniques have emerged for select cases with equivalent cancer specific survival (CSS). We present the largest series with longest follow-up to date of retrograde ureteroscopy as the primary treatment of UTUC. METHODS: A retrospective review was performed of 258 patients diagnosed with UTUC who were initially evaluated and managed by a single surgeon. Patients were followed from 1994 to 2017. Clinical records were evaluated for patient and tumor characteristics, operative parameters and outcomes. Statistical analysis was performed to identify risk of recurrence, progression, cancer and overall survival. RESULTS: Following exclusion criteria, 168 patients were evaluated. Average tumor size on initial excision was 16.8mm. Mean age of the cohort was 70 years, with mean follow-up of 5.53 years. The 5-year overall survival was 80.9%, but CSS was 92.6%. Recurrence free survival was 30% with average tumor size on recurrence of 6.39mm. Progression free survival was 75% with a renal preservation rate of 71.4%. CONCLUSIONS: Ureteroscopic management of UTUC is a successful alternative to nephroureterectomy in select cases of UTUC. With strict surveillance protocols to manage frequent local recurrence rates, it is possible to achieve high renal preservation rates with acceptable CSS, even in the long-term.

Dynamic pulmonary CT perfusion using first-pass analysis technique with only two volume scans: Validation in a swine model.

PURPOSE: To evaluate the accuracy of a low-dose first-pass analysis (FPA) CT pulmonary perfusion technique in comparison to fluorescent microsphere measurement as the reference standard. METHOD: The first-pass analysis CT perfusion technique was validated in six swine (41.7 ± 10.2 kg) for a total of 39 successful perfusion measurements. Different perfusion conditions were generated in each animal using serial balloon occlusions in the pulmonary artery. For each occlusion, over 20 contrast-enhanced CT images were acquired within one breath (320 x 0.5mm collimation, 100kVp, 200mA or 400mA, 350ms gantry rotation time). All volume scans were used for maximum slope model (MSM) perfusion measurement, but only two volume scans were used for the FPA measurement. Both MSM and FPA perfusion measurements were then compared to the reference fluorescent microsphere measurements. RESULTS: The mean lung perfusion of MSM, FPA, and microsphere measurements were 6.21 ± 3.08 (p = 0.008), 6.59 ± 3.41 (p = 0.44) and 6.68 ± 3.89 ml/min/g, respectively. The MSM (PMSM) and FPA (PFPA) perfusion measurements were related to the corresponding reference microsphere measurement (PMIC) by PMSM = 0.51PMIC + 2.78 (r = 0.64) and PFPA = 0.79PMIC + 1.32 (r = 0.90). The root-mean-square-error for the MSM and FPA techniques were 3.09 and 1.72 ml/min/g, respectively. The root-mean-square-deviation for the MSM and FPA techniques were 2.38 and 1.50 ml/min/g, respectively. The CT dose index for MSM and FPA techniques were 138.7 and 8.4mGy, respectively. CONCLUSIONS: The first-pass analysis technique can accurately measure regional pulmonary perfusion and has the potential to reduce the radiation dose associated with dynamic CT perfusion for assessment of pulmonary disease.

Vessel-specific coronary perfusion territories using a CT angiogram with a minimum cost path technique and its direct comparison to the American Heart Association 17-segment model.

OBJECTIVES: This study compared the accuracy of an automated, vessel-specific minimum cost path (MCP) myocardial perfusion territory assignment technique as compared with the standard American Heart Association 17-segment (AHA) model. METHODS: Six swine (42 ± 9 kg) were used to evaluate the accuracy of the MCP technique and the AHA method. In each swine, a dynamic acquisition, comprised of twenty consecutive whole heart volume scans, was acquired with a computed tomography scanner, following peripheral injection of contrast material. From this acquisition, MCP and AHA perfusion territories were determined, for the left (LCA) and right (RCA) coronary arteries. Each animal underwent additional dynamic acquisitions, consisting of twenty consecutive volume scans, following direct intracoronary contrast injection into the LCA or RCA. These images were used as the reference standard (REF) LCA and RCA perfusion territories. The MCP and AHA techniques' perfusion territories were then quantitatively compared with the REF perfusion territories. RESULTS: The myocardial mass of MCP perfusion territories (MMCP) was related to the mass of reference standard perfusion territories (MREF) by MMCP = 0.99MREF + 0.39 g (r = 1.00; R2 = 1.00). The mass of AHA perfusion territories (MAHA) was related to MREF by MAHA = 0.81MREF + 5.03 g (r = 0.99; R2 = 0.98). CONCLUSION: The vessel-specific MCP myocardial perfusion territory assignment technique more accurately quantifies LCA and RCA perfusion territories as compared with the current standard AHA 17-segment model. Therefore, it can potentially provide a more comprehensive and patient-specific evaluation of coronary artery disease. KEY POINTS: • The minimum cost path (MCP) technique accurately determines left and right coronary artery perfusion territories, as compared with the American Heart Association 17-segment (AHA) model. • The minimum cost path (MCP) technique could be applied to cardiac computed-tomography angiography images to accurately determine patient-specific left and right coronary artery perfusion territories. • The American Heart Association 17-segment (AHA) model often fails to accurately determine left and right coronary artery perfusion territories, especially in the inferior and inferoseptal walls of the left ventricular myocardium.

Low-Radiation-Dose Stress Myocardial Perfusion Measurement Using First-Pass Analysis Dynamic Computed Tomography: A Preliminary Investigation in a Swine Model.

OBJECTIVES: The aim of this study was to assess the feasibility of a prospective first-pass analysis (FPA) dynamic computed tomography (CT) perfusion technique for accurate low-radiation-dose global stress perfusion measurement. MATERIALS AND METHODS: The prospective FPA technique was evaluated in 10 swine (42 ± 12 kg) by direct comparison to a previously validated retrospective FPA technique. Of the 10 swine, 3 had intermediate stenoses with fractional flow reserve severities of 0.70 to 0.90. In each swine, contrast and saline were injected peripherally followed by dynamic volume scanning with a 320-slice CT scanner. Specifically, for the reference standard retrospective FPA technique, volume scans were acquired continuously at 100 kVp and 200 mA over 15 to 20 seconds, followed by systematic selection of only 2 volume scans for global perfusion measurement. For the prospective FPA technique, only 2 volume scans were acquired at 100 kVp and 50 mA for global perfusion measurement. All prospective global stress perfusion measurements were then compared with the corresponding reference standard retrospective global stress perfusion measurements through regression analysis. The CTDIvol and size-specific dose estimate of the prospective FPA technique were also determined. RESULTS: All prospective global stress perfusion measurements (PPRO) at 50 mA were in good agreement with the reference standard retrospective global stress perfusion measurements (PREF) at 200 mA (PPRO = 1.07 PREF -0.09, r = 0.94; root-mean-square error = 0.30 mL/min per gram). The CTDIvol and size-specific dose estimate of the prospective FPA technique were 2.3 and 3.7 mGy, respectively. CONCLUSIONS: Accurate low-radiation-dose global stress perfusion measurement is feasible using a prospective FPA dynamic CT perfusion technique.