Performance of an ultra-fast deep-learning accelerated MRI screening protocol for prostate cancer compared to a standard multiparametric protocol.

OBJECTIVES: To establish and evaluate an ultra-fast MRI screening protocol for prostate cancer (PCa) in comparison to the standard multiparametric (mp) protocol, reducing scan time and maintaining adequate diagnostic performance. MATERIALS AND METHODS: This prospective single-center study included consecutive biopsy-naïve patients with suspected PCa between December 2022 and March 2023. A PI-RADSv2.1 conform mpMRI protocol was acquired in a 3 T scanner (scan time: 25 min 45 sec). In addition, two deep-learning (DL) accelerated sequences (T2- and diffusion-weighted) were acquired, serving as a screening protocol (scan time: 3 min 28 sec). Two readers evaluated image quality and the probability of PCa regarding PI-RADSv2.1 scores in two sessions. The diagnostic performance of the screening protocol with mpMRI serving as the reference standard was derived. Inter- and intra-reader agreements were evaluated using weighted kappa statistics. RESULTS: We included 77 patients with 97 lesions (mean age: 66 years; SD: 7.7). Diagnostic performance of the screening protocol was excellent with a sensitivity and specificity of 100%/100% and 89%/98% (cut-off ≥ PI-RADS 4) for reader 1 (R1) and reader 2 (R2), respectively. Mean image quality was 3.96 (R1) and 4.35 (R2) for the standard protocol vs. 4.74 and 4.57 for the screening protocol (p < 0.05). Inter-reader agreement was moderate (κ: 0.55) for the screening protocol and substantial (κ: 0.61) for the multiparametric protocol. CONCLUSION: The ultra-fast screening protocol showed similar diagnostic performance and better imaging quality compared to the mpMRI in under 15% of scan time, improving efficacy and enabling the implementation of screening protocols in clinical routine. CLINICAL RELEVANCE STATEMENT: The ultra-fast protocol enables examinations without contrast administration, drastically reducing scan time to 3.5 min with similar diagnostic performance and better imaging quality. This facilitates patient-friendly, efficient examinations and addresses the conflict of increasing demand for examinations at currently exhausted capacities. KEY POINTS: Time-consuming MRI protocols are in conflict with an expected increase in examinations required for prostate cancer screening. An ultra-fast MRI protocol shows similar performance and better image quality compared to the standard protocol. Deep-learning acceleration facilitates efficient and patient-friendly examinations, thus improving prostate cancer screening capacity.

Improved diffusion-weighted imaging of the prostate: Comparison of readout-segmented and zoomed single-shot imaging.

OBJECTIVES: Diffusion weighted imaging (DWI) is the most important sequence for detection and grading prostate cancer (PCa), but it is considerably prone to artifacts. New approaches like zoomed single-shot imaging (z-EPI) with advanced image processing or multi-shot readout segmentation (rs-EPI) try to improve DWI quality. This study evaluates objective and subjective image quality (IQ) of rs-EPI and z-EPI with and without advanced processing. MATERIALS AND METHODS: Fifty-six consecutive patients (67 ± 8 years; median PSA 8.3 ng/ml) with mp-MRI performed at 3 Tesla between February and October 2019 and subsequently verified PCa by targeted plus systematic MRI/US-fusion biopsy were included in this retrospective single center cohort study. Rs-EPI and z-EPI were prospectively acquired in every patient. Signal intensities (SI) of PCa and benign tissue in ADC, b1000, and calculated high b-value images were analyzed. Endpoints were signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), PCa contrast intensity (CI), and subjective IQ on a 5-point scale evaluated by three blinded readers. Wilcoxon signed rank test, Friedman test and Cohen's kappa coefficient was calculated. RESULTS: SNR, CNR, and PCa CI of z-EPI with and without advanced processing was superior to rs-EPI (p < 0.01), whereas no significant differences were observed between z-EPI with and without advanced processing. Subjective IQ was significantly higher for z-EPI with advanced processing compared rs-EPI for ADC, b1000, and calculated high b-values (p < 0.01). Compared to z-EPI without advanced processing, z-EPI with advanced processing was superior for ADC and calculated high b-values (p < 0.01), but no significant differences were shown for b1000 images. CONCLUSIONS: Z-EPI with and without advanced processing was superior to rs-EPI regarding objective imaging parameters and z-EPI with advanced processing was superior to rs-EPI regarding subjective imaging parameters for the detection of PCa.

Neuromyelitis optica: a diffusional kurtosis imaging study.

BACKGROUND AND PURPOSE: Conventional MR imaging typically yields normal images of the brain or indicates lesions in areas of high aquaporin expression in patients with neuromyelitis optica. Diffusional kurtosis imaging was applied in patients with neuromyelitis optica to determine whether this technique could detect alterations in diffusion and diffusional kurtosis parameters in normal-appearing white matter and to explore the relationship between diffusional kurtosis imaging and DTI parameters. MATERIALS AND METHODS: Thirteen patients with neuromyelitis optica and 13 healthy controls underwent MR imaging of the brain with conventional and diffusional kurtosis imaging sequences. Tract-based spatial statistics and region-of-interest-based analyses were conducted to identify differences between patients with neuromyelitis optica and controls through conventional DTI and diffusional kurtosis imaging parameters. The parameters were correlated to determine the potential relationship between them. RESULTS: Compared with healthy controls, several diffusional kurtosis imaging and DTI parameters were altered in various fiber tracts of patients with neuromyelitis optica (P < .05). A significant decrease (P < .05) in radial kurtosis was observed in the corpus callosum and anterior corona radiata and left optic radiation. Differences (P < .1) in mean kurtosis were found in patients with neuromyelitis optica. We found a negative correlation between diffusional kurtosis imaging (radial kurtosis, axial kurtosis, mean kurtosis) and the corresponding DTI parameters (radial diffusivity, axial diffusivity, mean diffusivity). Positive correlations were found for radial kurtosis and mean kurtosis with fractional anisotropy. CONCLUSIONS: This study demonstrated differences in conventional diffusion and diffusional kurtosis parameters, especially radial kurtosis, in the normal-appearing white matter of patients with neuromyelitis optica compared with healthy controls. Larger studies of patients with neuromyelitis optica should be performed to assess the potential clinical impact of these findings.

Sleep active cortical neurons expressing neuronal nitric oxide synthase are active after both acute sleep deprivation and chronic sleep restriction.

Non-rapid eye movement (NREM) sleep electroencephalographic (EEG) delta power (~0.5-4 Hz), also known as slow wave activity (SWA), is typically enhanced after acute sleep deprivation (SD) but not after chronic sleep restriction (CSR). Recently, sleep-active cortical neurons expressing neuronal nitric oxide synthase (nNOS) were identified and associated with enhanced SWA after short acute bouts of SD (i.e., 6h). However, the relationship between cortical nNOS neuronal activity and SWA during CSR is unknown. We compared the activity of cortical neurons expressing nNOS (via c-Fos and nNOS immuno-reactivity, respectively) and sleep in rats in three conditions: (1) after 18-h of acute SD; (2) after five consecutive days of sleep restriction (SR) (18-h SD per day with 6h ad libitum sleep opportunity per day); (3) and time-of-day matched ad libitum sleep controls. Cortical nNOS neuronal activity was enhanced during sleep after both 18-h SD and 5 days of SR treatments compared to control treatments. SWA and NREM sleep delta energy (the product of NREM sleep duration and SWA) were positively correlated with enhanced cortical nNOS neuronal activity after 18-h SD but not 5days of SR. That neurons expressing nNOS were active after longer amounts of acute SD (18h vs. 6h reported in the literature) and were correlated with SWA further suggest that these cells might regulate SWA. However, since these neurons were active after CSR when SWA was not enhanced, these findings suggest that mechanisms downstream of their activation are altered during CSR.

c-Fos protein expression is increased in cholinergic neurons of the rodent basal forebrain during spontaneous and induced wakefulness.

It has been proposed that cholinergic neurons of the basal forebrain (BF) may play a role in vigilance state control. Since not all vigilance states have been studied, we evaluated cholinergic neuronal activation levels across spontaneously occurring states of vigilance, as well as during sleep deprivation and recovery sleep following sleep deprivation. Sleep deprivation was performed for 2h at the beginning of the light (inactive) period, by means of gentle sensory stimulation. In the rodent BF, we used immunohistochemical detection of the c-Fos protein as a marker for activation, combined with labeling for choline acetyl-transferase (ChAT) as a marker for cholinergic neurons. We found c-Fos activation in BF cholinergic neurons was highest in the group undergoing sleep deprivation (12.9% of cholinergic neurons), while the spontaneous wakefulness group showed a significant increase (9.2%), compared to labeling in the spontaneous sleep group (1.8%) and a sleep deprivation recovery group (0.8%). A subpopulation of cholinergic neurons expressed c-Fos during spontaneous wakefulness, when possible confounds of the sleep deprivation procedure were minimized (e.g., stress and sensory stimulation). Double-labeling in the sleep deprivation treatment group was significantly elevated in select subnuclei of the BF (medial septum/vertical limb of the diagonal band, horizontal limb of the diagonal band, and the magnocellular preoptic nucleus), when compared to spontaneous wakefulness. These findings support and provide additional confirming data of previous reports that cholinergic neurons of BF play a role in vigilance state regulation by promoting wakefulness.

Sleep fragmentation elevates behavioral, electrographic and neurochemical measures of sleepiness.

Sleep fragmentation, a feature of sleep apnea as well as other sleep and medical/psychiatric disorders, is thought to lead to excessive daytime sleepiness. A rodent model of sleep fragmentation was developed (termed sleep interruption, SI), where rats were awakened every 2 min by the movement of an automated treadmill for either 6 or 24 h of exposure. The sleep pattern of rats exposed to 24 h of SI resembled sleep of the apneic patient in the following ways: sleep was fragmented (up to 30 awakening/h), total rapid eye movement (REM) sleep time was greatly reduced, non-rapid eye movement (NREM) sleep episode duration was reduced (from 2 min, 5 s baseline to 58 s during SI), whereas the total amount of NREM sleep time per 24 h approached basal levels. Both 6 and 24 h of SI made rats more sleepy, as indicated by a reduced latency to fall asleep upon SI termination. Electrographic measures in the recovery sleep period following either 6 or 24 h of SI also indicated an elevation of homeostatic sleep drive; specifically, the average NREM episode duration increased (e.g. for 24 h SI, from 2 min, 5 s baseline to 3 min, 19 s following SI), as did the NREM delta power during recovery sleep. Basal forebrain (BF) levels of extracellular adenosine (AD) were also measured with microdialysis sample collection and high performance liquid chromatography detection, as previous work suggests that increasing concentrations of BF AD are related to sleepiness. BF AD levels were significantly elevated during SI, peaking at 220% of baseline during 30 h of SI exposure. These combined findings imply an elevation of the homeostatic sleep drive following either 6 or 24 h of SI, and BF AD levels appear to correlate more with sleepiness than with the cumulative amount of prior wakefulness, since total NREM sleep time declined only slightly. SI may be partially responsible for the symptom of daytime sleepiness observed in a number of clinical disorders, and this may be mediated by mechanisms involving BF AD.

High resolution 3 Tesla contrast-enhanced MR angiography of the hands in Raynaud's disease.

Raynaud's disease is associated with disorders in blood circulation of the hands. The gold standard to visualise pathology of digital arteries is catheter angiography. Contrast-enhanced MR angiography (CE MRA) has developed even more as an alternative non-invasive method to digital subtraction angiography, mostly for pelvic or lower limb vessels. We report a case of primary Raynaud's disease with high-grade stenosis and an occlusion of the digital arteries. This case illustrates the benefit and efficiency of CE MRA at high fields in depicting location and extension of peripheral arterial alterations.

Differential effect of orexins (hypocretins) on serotonin release in the dorsal and median raphe nuclei of freely behaving rats.

Orexin (hypocretin)-containing neurons in the perifornical hypothalamus project to widespread regions of the brain, including the dorsal and median raphe nuclei [Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18:9996-10015; Wang QP, Koyama Y, Guan JL, Takahashi K, Kayama Y, Shioda S (2005) The orexinergic synaptic innervation of serotonin- and orexin 1-receptor-containing neurons in the dorsal raphe nucleus. Regul Pept 126:35-42]. Orexin-A or orexin-B was infused by reverse microdialysis into the dorsal raphe nucleus or median raphe nucleus of freely behaving rats, and extracellular serotonin was simultaneously collected by microdialysis and analyzed by high-performance liquid chromatography. We have found that orexin-A produced a dose-dependent increase of serotonin in the dorsal raphe nucleus, but not in the median raphe nucleus. However, orexin-B elicited a small but significant effect in both the dorsal raphe nucleus and median raphe nucleus. Orexins may have regionally selective effects on serotonin release in the CNS, implying a unique interaction between orexins and serotonin in the regulation of activities including sleep-wakefulness.

Effects on serotonin of (-)nicotine and dimethylphenylpiperazinium in the dorsal raphe and nucleus accumbens of freely behaving rats.

The aim of this study was to investigate the neurochemical mechanism underlying the effect of nicotine and dimethylphenylpiperazinium (DMPP) on 5-hydroxytryptamine (5-HT) release in the dorsal raphe nucleus and nucleus accumbens of freely behaving rats. For comparison, lobeline, cytisine and RJR-2403 were also investigated. It was found that all drugs, when infused locally, evoked an increase of 5-HT in the dorsal raphe nucleus. However, the magnitudes of the 5-HT increase were comparatively different between the drugs in the ranking of their potency: DMPP>RJR 2403>>nicotine>lobeline>cytisine. Both methyllycaconitine, a nicotinic acetylcholine receptor (nAChR) antagonist and methyllycaconitine, a selective alpha7-containing nAChR antagonist blocked the effects of nicotine and DMPP, suggesting that alpha7 subunit mediated the increases in 5-HT. However, DMPP was reported to increase 5-HT using non-nAChR mechanism [Lendvai B, Sershen H, Lajtha A, Santha E, Baranyi M, Vizi ES (1996) Differential mechanisms involved in the effect of nicotinic agonists DMPP and lobeline to release [3H]5-HT from rat hippocampal slices. Neuropharmacology 35:1769-1777]. To test if 5-HT carriers were involved, a selective 5-HT reuptake inhibitor citalopram (1 microM) was infused into the dorsal raphe nucleus before administration of nicotine or DMPP. As a result, citalopram significantly blocked the effect of DMPP, whereas it had no influence on nicotine. Finally, the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was used to test whether the increases in 5-HT were depolarization-dependent. Administration of 8-OH-DPAT (0.1 mg/kg, s.c.) produced significant decreases in 5-HT in the animals treated with nicotine. In contrast, the effect of DMPP was not altered by 8-OH-DPAT, suggesting that the increases in 5-HT were independent of cell membrane depolarization. In conclusion, there are different mechanisms involved in nicotine- and DMPP-evoked increases in 5-HT. This is consistent with prior work suggesting DMPP may primarily act on 5-HT carriers.

Dynamic 3D MR angiography of intra- and extracranial vascular malformations at 3T: a technical note.

Time-resolved, contrast-enhanced 3D MR angiography combined with parallel imaging at 3T was applied to an intracranial arteriovenous malformation, a dural arteriovenous fistula, and an extracranial facial arteriovenous malformation. The temporal resolution was one image every 1.5 seconds. Arterial feeders were depicted in all three cases. Early venous drainage was observed in the intracerebral arteriovenous malformation and the dural arteriovenous fistula, but not in the facial arteriovenous malformation. All findings were concordant with conventional angiography.

Vessel size imaging in humans.

The relation of contrast-enhanced transverse relaxation rates R2* and R2 provides in vivo mapping of the mean caliber of cerebral vessels. This technique is referred to as vessel size imaging (VSI). Here a quantitative assessment of the vessel caliber in brain tumor patients is presented. The obtained mean vessel size shows sensitivity to the tumor type. A theoretical analysis is given to elucidate the morphological information content of VSI in the context of vessel architecture. The simplification of the theory underlying the data processing results in a systematic overestimation of the vessel caliber. An increase in the magnetic susceptibility of the contrast agent allows for quantitatively more accurate measurements. Quantitative VSI must include measurements of the regional diffusion coefficient and absolute determination of the regional cerebral blood volume.

Parkes Weber or Klippel-Trenaunay syndrome? Non-invasive diagnosis with MR projection angiography.

Klippel-Trenaunay and Parkes Weber (Klippel-Trenaunay-Weber) syndromes consist of vascular malformations of the capillary, venous and lymphatic systems combined with soft tissue and bone hypertrophy of the affected extremity. Klippel-Trenaunay syndrome is a pure low-flow condition, while Parkes Weber syndrome is characterized by significant arteriovenous fistulas. The distinction of both entities is relevant, since the prognosis and therapeutic strategies differ significantly. Our purpose is to demonstrate that thick-slice dynamic magnetic resonance projection angiography (MRPA) is a non-invasive tool to detect arteriovenous shunting in Parkes Weber syndrome. Four patients underwent MR imaging and MRPA. MRPA demonstrated arteriovenous shunting in three patients. Arteriovenous shunting was characterized by early appearing draining veins. The time of arrival between normal arteries and pathological veins varied between less than 0.5 and 1.0 s. Therefore, the diagnosis in these cases could be specified as Parkes Weber syndrome. In all these cases, arteriovenous shunting was confirmed by intraarterial digital subtraction angiography. One patient showed normal results in MRPA and could be diagnosed as having Klippel-Trenaunay syndrome.

Adenosinergic inhibition of basal forebrain wakefulness-active neurons: a simultaneous unit recording and microdialysis study in freely behaving cats.

The majority of neurons in the magnocellular basal forebrain are wakefulness-active with highest discharge activity during wakefulness and a marked reduction in activity just before and during the entry to non-rapid eye movement (REM) sleep. We have hypothesized that the reduction of discharge activity of wakefulness-active neurons and a consequent facilitation of the transition from wakefulness to sleep is due to an increase in the extracellular concentration of adenosine during wakefulness. To test the hypothesis, the present study employed microdialysis perfusion of adenosinergic pharmacological agents combined with single unit recording in freely moving cats, so as to determine: 1). if there were dose-dependent effects on behaviorally identified wakefulness-active neurons; 2). whether effects were mediated by the A1 receptor, as contrasted to the A2a receptor; and 3). if effects were specific to wakefulness-active neurons, and not present in sleep-active neurons, those preferentially discharging in nonREM sleep. Both adenosine and the A1 receptor-specific agonist N6-cyclo-hexyl-adenosine reduced the discharge activity of wakefulness-active neurons (n=16) in a dose-dependent manner but had no effect on sleep-active neurons (n=4). The A1 receptor antagonist 8-cyclopentyl-1-3-dimethylxanthine increased the discharge of wakefulness-active neurons (n=5), but the A2a receptor agonist, CGS-16284, had no effect (n=3). Recording sites were histologically localized to the cholinergic basal forebrain. These data support our hypothesis that adenosine acts via the A1 receptor to reduce the activity of wakefulness-promoting neurons, thus providing a cellular mechanism explaining why the increased adenosine concentrations observed in the basal forebrain following prolonged wakefulness act to induce sleep.

Head and neck vascular malformations: time-resolved MR projection angiography.

Extracranial vascular anomalies can be divided into haemangiomas and vascular malformations. The latter can be subdivided on the basis of the predominant type of vascular channels. Separation of high- and low-flow vascular malformations is of clinical importance. We report preliminary observations on time-resolved magnetic resonance projection angiography (MRPA) of vascular malformations of the head and neck. We examined eight patients with vascular anomalies of the head and neck. On MRPA the time between the early arterial phase and enhancement of the malformation could be used to distinguish high- and low-flow lesions. High-flow arteriovenous malformations showed early, intense enhancement. Venous malformations were either not visible on MRPA or showed late enhancement of veins. One patient was examined after embolisation of an arteriovenous fistula of the mandible. Normal MRPA was taken to indicate absence of a residual lesion.

Background suppression using magnetization preparation for contrast-enhanced 3D MR angiography of the pelvic and lower leg arteries.

PURPOSE: To develop and evaluate non-slab-selective magnetization preparation in contrast-enhanced 3D-MR angiography. METHODS: An ultrafast spoiled mr angiography sequence (FLASH) with non-selective inversion prepulses for background suppression was implemented on a 1.5 T MR system. In 11 patients gadobenate dimeglumine-enhanced mr-angiography of the pelvic and lower leg arteries was performed using the AngioSURF device. Source data was evaluated for contrast-to-noise-ratio, image quality and the extent of background suppression. RESULTS: Background suppression and selective vessel contrast was excellent in all vascular levels. The mr protocol was comfortable and easy-to-handle. Abandonment of precontrast-series acquisition simplified the examination procedure markedly. CONCLUSIONS: Magnetization preparation provides efficient suppression of the background signal in contrast-enhanced 3D mr angiography of the pelvic and lower leg arteries. Since no subtraction technique is needed, moving-bed and whole body MRA-protocols can be simplified significantly.

Ventrolateral preoptic nucleus contains sleep-active, galaninergic neurons in multiple mammalian species.

The ventrolateral preoptic nucleus (VLPO) is a group of sleep-active neurons that has been identified in the hypothalamus of rats and is thought to inhibit the major ascending monoaminergic arousal systems during sleep; lesions of the VLPO cause insomnia. Identification of the VLPO in other species has been complicated by the lack of a marker for this cell population, other than the expression of Fos during sleep. We now report that a high percentage of the sleep-active (Fos-expressing) VLPO neurons express mRNA for the inhibitory neuropeptide, galanin, in nocturnal rodents (mice and rats), diurnal rodents (degus), and cats. A homologous (i.e. galanin mRNA-containing cell group) is clearly distinguishable in the ventrolateral region of the preoptic area in diurnal and nocturnal monkeys, as well as in humans. Galanin expression may serve to identify sleep-active neurons in the ventrolateral preoptic area of the mammalian brain. The VLPO appears to be a critical component of sleep circuitry across multiple species, and we hypothesize that shrinkage of the VLPO with advancing age may explain sleep deficits in elderly humans.

Extracellular histamine levels in the feline preoptic/anterior hypothalamic area during natural sleep-wakefulness and prolonged wakefulness: an in vivo microdialysis study.

Increased activity of the histaminergic neurons of the posterior hypothalamus has been implicated in the facilitation of behavioral wakefulness. Recent evidence of reciprocal projections between the sleep-active neurons of the preoptic/anterior hypothalamus and the histaminergic neurons of the tuberomammillary nucleus suggests that histaminergic innervation of the preoptic/anterior hypothalamic area may be of particular importance in the wakefulness-promoting properties of histamine. To test this possibility, we used microdialysis sample collection in the preoptic/anterior hypothalamic area of cats during natural sleep-wakefulness cycles, 6 h of sleep deprivation induced by gentle handling/playing, and recovery sleep. Samples were analyzed by a sensitive radioenzymatic assay. Mean basal levels of histamine in microdialysate during periods of wakefulness (1.155+/-0.225 pg/microl) did not vary during the 6 h of sleep deprivation. However, during the different sleep states, dramatic changes were observed in the extracellular histamine levels of preoptic/anterior hypothalamic area: wakefulness>non-rapid eye movement sleep>rapid eye movement sleep. Levels of histamine during rapid eye movement sleep were lowest (0.245+/-0.032 pg/microl), being significantly lower than levels during non-rapid eye movement sleep (0.395+/-0.081 pg/microl) and being only 21% of wakefulness levels. This pattern of preoptic/anterior hypothalamic area extracellular histamine levels across the sleep-wakefulness cycle closely resembles the reported single unit activity of histaminergic neurons. However, the invariance of histamine levels during sleep deprivation suggests that changes in histamine level do not relay information about sleep drive to the sleep-promoting neurons of the preoptic/anterior hypothalamic area.

Dynamic time-resolved contrast-enhanced two-dimensional MR projection angiography of the pulmonary circulation: standard technique and clinical applications.

OBJECTIVE: Time-resolved pulmonary two-dimensional MR projection angiography is a fast acquisition technique that allows the generation of dynamic projection angiograms by a method similar to that used to generate digital subtraction angiograms. MR images are obtained after subtracting the mask defined at the beginning of the sequence from later images, thus generating time-resolved continuous projection angiograms that depict the passage of a bolus through the pulmonary circulation. This article describes the application of this novel technique in three patients with pathologic conditions not previously described with this modality and two control subjects. CONCLUSION: The analysis of the findings on dynamic time-resolved contrast-enhanced two-dimensional MR projection angiography shows that this technique is useful not only in revealing morphologic changes associated with pulmonary disorders but also in following the passage of the bolus through the cardiopulmonary circulation. The latter capability allows qualitative detection of normal or abnormal pathways and thus is potentially of value in the assessment of several pulmonary disorders.