Dual-energy CT for liver iron quantification in patients with haematological disorders.

OBJECTIVES: To retrospectively quantify liver iron content in haematological patients suspected of transfusional haemosiderosis using dual-energy CT (DECT) and correlate with serum ferritin levels and estimated quantity of transfused iron. METHODS: One hundred forty-seven consecutive dual-source dual-energy non-contrast chest-CTs in 110 haematologic patients intended primarily for exclusion of pulmonary infection between September 2016 and June 2017 were retrospectively evaluated. Image data was post-processed with a software prototype. After material decomposition, an iron enhancement map was created and freehand ROIs were drawn including most of the partially examined liver. The virtual iron content (VIC) was calculated and expressed in milligram/millilitre. VIC was correlated with serum ferritin and estimated amount of transfused iron. Scans of patients who had not received blood products were considered controls. RESULTS: Forty-eight (32.7%) cases (controls) had not received any blood transfusions whereas 67.3% had received one transfusion or more. Median serum ferritin and VIC were 138.0 µg/dl (range, 6.0-2628.0 µg/dl) and 1.33 mg/ml (range, - 0.94-7.56 mg/ml) in the post-transfusional group and 27.0 µg/dl (range, 1.0-248.0 µg/dl) and 0.61 mg/ml (range, - 2.1-2.4) in the control group. Correlation between serum ferritin and VIC was strong (r = 0.623; p < 0.001) as well as that between serum ferritin and estimated quantity of transfused iron (r = 0.681; p < 0.001). CONCLUSIONS: Hepatic VIC obtained via dual-energy chest-CT examinational protocol strongly correlates with serum ferritin levels and estimated amount of transfused iron and could therefore be used in the routine diagnosis for complementary evaluation of transfusional haemosiderosis. KEY POINTS: • Virtual liver iron content was measured in routine chest-CTs of haematological patients suspected of having iron overload. Chest-CTs were primarily intended for exclusion of pulmonary infection. • Measurements correlate strongly with the most widely used blood marker of iron overload serum ferritin (after exclusion of infection) and the amount of transfused iron. • Liver VIC could be used for supplemental evaluation of transfusional haemosiderosis in haematological patients.

Viral infection risks for patients using the finished product Hirudo verbana (medicinal leech).

The virological safety of medicinal leeches has to be ensured prior to their use on patients. While leeches can be kept and bred under standardized conditions, feeding them horse blood adds a non-standardized component, which poses some risk of infection of the treated patients. Here, we investigated the speed at which blood-borne viruses are degraded by the microbial flora in the leech intestine, in order to define the safety of the product and the length of the necessary quarantine period prior to its administration to patients. Feeding blood was spiked with bovine viral diarrhea virus (BVDV), reovirus, and murine parvovirus (10(7) ID50 ml(-1)). The virus titer in the intestinal contents of the leeches was determined using permissive cell cultures and compared to that of the original virus titer at the following time points: immediately after feeding; after 3, 14, and 30 days; and monthly thereafter until the 7th month. The BVDV titer was below the detection limit of 10(1) TCID50 ml(-1) after 3 months, while reovirus and murine parvovirus titers were undetectable after 4 months. No positive virus findings were obtained at later time points. Thus, when fed the blood of vertebrates, the finished product "Medicinal leech, Hirudo verbana" can be considered virologically safe if the animals are maintained at 20 °C, which corresponds to their natural habitat conditions and ensures a high metabolic rate. Therefore, after the last feeding, a quarantine period of 4-6 months and appropriate care at room temperature, which supports microbial degradation and digestive processes, are recommended.

Effects of parietal TMS on visual and auditory processing at the primary cortical level -- a concurrent TMS-fMRI study.

Accumulating evidence suggests that multisensory interactions emerge already at the primary cortical level. Specifically, auditory inputs were shown to suppress activations in visual cortices when presented alone but amplify the blood oxygen level-dependent (BOLD) responses to concurrent visual inputs (and vice versa). This concurrent transcranial magnetic stimulation-functional magnetic resonance imaging (TMS-fMRI) study applied repetitive TMS trains at no, low, and high intensity over right intraparietal sulcus (IPS) and vertex to investigate top-down influences on visual and auditory cortices under 3 sensory contexts: visual, auditory, and no stimulation. IPS-TMS increased activations in auditory cortices irrespective of sensory context as a result of direct and nonspecific auditory TMS side effects. In contrast, IPS-TMS modulated activations in the visual cortex in a state-dependent fashion: it deactivated the visual cortex under no and auditory stimulation but amplified the BOLD response to visual stimulation. However, only the response amplification to visual stimulation was selective for IPS-TMS, while the deactivations observed for IPS- and Vertex-TMS resulted from crossmodal deactivations induced by auditory activity to TMS sounds. TMS to IPS may increase the responses in visual (or auditory) cortices to visual (or auditory) stimulation via a gain control mechanism or crossmodal interactions. Collectively, our results demonstrate that understanding TMS effects on (uni)sensory processing requires a multisensory perspective.

Perceptual decisions formed by accumulation of audiovisual evidence in prefrontal cortex.

To form perceptual decisions in our multisensory environment, the brain needs to integrate sensory information derived from a common source and segregate information emanating from different sources. Combining fMRI and psychophysics in humans, we investigated how the brain accumulates sensory evidence about a visual source in the context of congruent or conflicting auditory information. In a visual selective attention paradigm, subjects (12 females, 7 males) categorized video clips while ignoring concurrent congruent or incongruent soundtracks. Visual and auditory information were reliable or unreliable. Our behavioral data accorded with accumulator models of perceptual decision making, where sensory information is integrated over time until a criterion amount of information is obtained. Behaviorally, subjects exhibited audiovisual incongruency effects that increased with the variance of the visual and the reliability of the interfering auditory input. At the neural level, only the left inferior frontal sulcus (IFS) showed an "audiovisual-accumulator" profile consistent with the observed reaction time pattern. By contrast, responses in the right fusiform were amplified by incongruent auditory input regardless of sensory reliability. Dynamic causal modeling showed that these incongruency effects were mediated via connections from auditory cortex. Further, while the fusiform interacted with IFS in an excitatory recurrent loop that was strengthened for unreliable task-relevant visual input, the IFS did not amplify and even inhibited superior temporal activations for unreliable auditory input. To form decisions that guide behavioral responses, the IFS may accumulate audiovisual evidence by dynamically weighting its connectivity to auditory and visual regions according to sensory reliability and decisional relevance.

Distinct functional contributions of primary sensory and association areas to audiovisual integration in object categorization.

Multisensory interactions have been demonstrated in a distributed neural system encompassing primary sensory and higher-order association areas. However, their distinct functional roles in multisensory integration remain unclear. This functional magnetic resonance imaging study dissociated the functional contributions of three cortical levels to multisensory integration in object categorization. Subjects actively categorized or passively perceived noisy auditory and visual signals emanating from everyday actions with objects. The experiment included two 2 x 2 factorial designs that manipulated either (1) the presence/absence or (2) the informativeness of the sensory inputs. These experimental manipulations revealed three patterns of audiovisual interactions. (1) In primary auditory cortices (PACs), a concurrent visual input increased the stimulus salience by amplifying the auditory response regardless of task-context. Effective connectivity analyses demonstrated that this automatic response amplification is mediated via both direct and indirect [via superior temporal sulcus (STS)] connectivity to visual cortices. (2) In STS and intraparietal sulcus (IPS), audiovisual interactions sustained the integration of higher-order object features and predicted subjects' audiovisual benefits in object categorization. (3) In the left ventrolateral prefrontal cortex (vlPFC), explicit semantic categorization resulted in suppressive audiovisual interactions as an index for multisensory facilitation of semantic retrieval and response selection. In conclusion, multisensory integration emerges at multiple processing stages within the cortical hierarchy. The distinct profiles of audiovisual interactions dissociate audiovisual salience effects in PACs, formation of object representations in STS/IPS and audiovisual facilitation of semantic categorization in vlPFC. Furthermore, in STS/IPS, the profiles of audiovisual interactions were behaviorally relevant and predicted subjects' multisensory benefits in performance accuracy.

Superadditive responses in superior temporal sulcus predict audiovisual benefits in object categorization.

Merging information from multiple senses provides a more reliable percept of our environment. Yet, little is known about where and how various sensory features are combined within the cortical hierarchy. Combining functional magnetic resonance imaging and psychophysics, we investigated the neural mechanisms underlying integration of audiovisual object features. Subjects categorized or passively perceived audiovisual object stimuli with the informativeness (i.e., degradation) of the auditory and visual modalities being manipulated factorially. Controlling for low-level integration processes, we show higher level audiovisual integration selectively in the superior temporal sulci (STS) bilaterally. The multisensory interactions were primarily subadditive and even suppressive for intact stimuli but turned into additive effects for degraded stimuli. Consistent with the inverse effectiveness principle, auditory and visual informativeness determine the profile of audiovisual integration in STS similarly to the influence of physical stimulus intensity in the superior colliculus. Importantly, when holding stimulus degradation constant, subjects' audiovisual behavioral benefit predicts their multisensory integration profile in STS: only subjects that benefit from multisensory integration exhibit superadditive interactions, while those that do not benefit show suppressive interactions. In conclusion, superadditive and subadditive integration profiles in STS are functionally relevant and related to behavioral indices of multisensory integration with superadditive interactions mediating successful audiovisual object categorization.