Diagnostic approach to focal liver lesions at cross-sectional imaging: a primer for beginners.

Liver imaging encompasses a broad spectrum of diseases in different clinical backgrounds. The available literature is vast and reported data often lacks standardization. Because of all these issues, the differential diagnosis and the characterization of liver lesions can be challenging for the beginner. The aim of this narrative review is to provide the basics for an algorithm approach to liver lesions on cross-sectional imaging. First, some tips for the optimization of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) protocols will be provided. Liver Imaging Reporting and Data System (LI-RADS, version 2018) working group is proposing the adoption of their standardized lexicon beyond the original target population of LI-RADS (i.e., liver cirrhosis). Thus, the main imaging findings will be defined following the LI-RADS lexicon. Since the contrast study is the most important for lesion characterization, this narrative review separates the lesions into avascular, hypovascular, and hypervascular, with a focus on chronic liver disease (CLD) and hepatocellular carcinoma (HCC).

Technological advances in body CT: a primer for beginners.

Many technological advances have entered the clinical routine of Computed Tomography (CT) imaging. The new CT scanners have specific solutions in gantry design to bear the mechanical solicitations. The X-ray tubes have been improved for faster acquisitions at low radiation exposure, while the innovations in CT detectors provide a better image quality. The optimization of image quality and contrast, and the reduction of radiation dose, cannot be achieved without the implementation of adequate reconstruction software, such as Iterative Reconstructions (IR) and Artificial Intelligence (AI). In recent years, dual-energy (DECT) technology has expanded the indications of CT. In this narrative review, a panoramic overview of the technological novelties in CT imaging will be provided for optimal utilization of CT technology.

Hepatic Arterial Embolization Using Cone Beam CT with Tumor Feeding Vessel Detection Software: Impact on Hepatocellular Carcinoma Response.

PURPOSE: Dedicated tumor feeding vessel detection software (TFVDS) using cone beam CT has shown a higher sensitivity to detect tumor feeding vessels during hepatic arterial embolization (HAE) of hepatocellular carcinoma (HCC) compared to 2D imaging. Our primary hypothesis was that HCC tumors treated with HAE guided by a TFVDS would show more complete response (CR) than when treated with 2D imaging alone. Secondary analysis of the impact on X-ray exposure was performed. MATERIALS AND METHODS: Nineteen males and 8 females (median age: 69 year, 46-85) with 44 tumors (median size: 38 mm, 6-100) treated with selective HAE between January 2013 and December 2014 were included. Exclusion criteria were: extra-hepatic supply, >4 tumors, tumor size >10 cm, and adjunctive local therapy. Baseline patient and procedure characteristics were reviewed. Differences in CR per modified Response Evaluation Criteria in Solid Tumors were assessed by univariate and multivariate analyses for tumor size, number, location, particles size, and use of TFVDS. RESULTS: Median imaging follow-up was 20.1 months (2-33). Use of TFVDS (13 patients, 19 tumors) was the only factor predictive of CR (OR = 3.85 [CI95%: 1.09, 13.67], p = 0.04) on univariate analysis but not on multivariate analysis (OR = 3.26 [0.87, 12.23], p = 0.08). A higher rate of CR was observed for HAE using TFVDS guidance versus 2D imaging alone (68.4%, 13-19, vs. 36%, 9-25, p = 0.03). Median dose area product was lower when TFVDS was used (149.7 Gy.cm2, 38-365, vs. 227.8 Gy.cm2, 85.3-468.6, p = 0.05). CONCLUSIONS: HCC embolized with TFVDS may result in improved local tumor response without increasing the dose exposure.

Audio-visual integration effect in lateral occipital cortex during an object recognition task: An interference pilot study.

BACKGROUND: Recent neuroimaging data support the hypothesis of a multisensory interplay at low-level sensory-specific cortex. OBJECTIVE: We used an on-line interference approach by rTMS to investigate the role of the left lateral occipital cortex (LOC) in audio-visual (AV) object recognition process. METHODS: Fifteen healthy volunteers performed a visual identification task of degraded pictures presented alone or simultaneously to coherent or non-coherent sounds. Focal 10-Hz rTMS at an intensity of 100% resting motor threshold was delivered simultaneously to the picture. Two blocks of 60 pictures were randomly displayed in two different experimental conditions: rTMS of the left LOC and over Cz. RESULTS: rTMS of the left LOC produced a worsening of the accuracy compared to rTMS over Cz specifically in the coherent AV condition. CONCLUSION: These data support the view that audio-visual interaction effect may occur at early stage of recognition processing.

Mild cognitive impairment: loss of linguistic task-induced changes in motor cortex excitability.

BACKGROUND: In amnestic mild cognitive impairment (aMCI), functional neuronal connectivity may be altered, as suggested by quantitative EEG and neuroimaging data. In young healthy humans, the execution of linguistic tasks modifies the excitability of the hand area of the dominant primary motor cortex (M1(hand)), as tested by transcranial magnetic stimulation (TMS). We used TMS to investigate functional connectivity between language-related cortical areas and M1(hand) in aMCI. METHODS: Ten elderly women with aMCI and 10 age-matched women were recruited. All participants were right handed and underwent a neuropsychological evaluation. In the first TMS experiment, participants performed three different tasks: reading aloud, viewing of non-letter strings (baseline), and nonverbal oral movements. The second experiment included the baseline condition and three visual searching/matching tasks using letters, geometric shapes, or digits as target stimuli. RESULTS: In controls, motor evoked potentials (MEP) elicited by suprathreshold TMS of the left M1(hand) were significantly larger during reading aloud (170% baseline) than during nonverbal oral movements, whereas no difference was seen for right M1(hand) stimulation. Similarly, MEP elicited by left M1(hand) stimulation during letter and shape searching/matching tasks were significantly larger compared to digit task. In contrast, linguistic task performance did not produce any significant MEP modulation in patients with aMCI, although neuropsychological evaluation showed normal language abilities. CONCLUSIONS: Findings suggest that functional connectivity between the language-related brain regions and the dominant M1(hand) may be altered in amnestic mild cognitive impairment. Follow-up studies will reveal whether transcranial magnetic stimulation application during linguistic tasks may contribute to characterize the risk of conversion to Alzheimer disease.

Role of the right dorsal premotor cortex in "physiological" mirror EMG activity.

A distributed cortical network enables the lateralization of intended unimanual movements, i.e., the transformation from a default mirror movement to a unimanual movement. Little is known about the exact functional organization of this "non-mirror transformation" network. Involvement of the right dorsal premotor cortex (dPMC) was suggested because its virtual lesion by high-frequency repetitive transcranial magnetic stimulation (rTMS) increased the excitability of the left primary motor cortex (M1) during unilateral isometric contraction of a left hand muscle (Cincotta et al., Neurosci Lett 367: 189-93, 2004). However, no behavioural effects were observed in that experimental protocol. Here we tested behaviourally twelve healthy volunteers to find out whether focal disruption of the right dPMC by "off-line" One Hz rTMS (900 pulses, 115% of resting motor threshold) enhances "physiological" mirroring. This was measured by an established protocol (Mayston et al., Ann Neurol 45: 583-94, 1999) that quantifies the mirror increase in the electromyographic (EMG) level in the isometrically contracting abductor pollicis brevis (APB) muscle of one hand during brief phasic contractions performed with the APB of the other hand. Mirroring in the right APB significantly increased after real rTMS of the right dPMC. In contrast, no change in mirroring was seen with sham rTMS of the right dPMC, real rTMS of the right M1, or real rTMS of the left dPMC. These findings strongly support the hypothesis that the right dPMC is part of the non-mirror transformation cortical network.

Modulatory effects of high-frequency repetitive transcranial magnetic stimulation on the ipsilateral silent period.

In healthy subjects, suprathreshold repetitive transcranial magnetic stimulation (rTMS) at frequencies >2 Hz prolongs the cortical silent period (CSP) over the course of the train. This progressive lengthening probably reflects temporal summation of the inhibitory interneurons in the stimulated primary motor cortex (M1). In this study, we tested whether high-frequency rTMS also modulates the ipsilateral silent period (ISP). In nine normal subjects, suprathreshold 10-pulse rTMS trains were delivered to the right M1 at frequencies of 3, 5, and 10 Hz during maximal isometric contraction of both first dorsal interosseous muscles. At 10 Hz, the second pulse of the train increased the area of the ISP; the other stimuli did not increase it further. During rTMS at 3 and 5 Hz, the ISP remained significantly unchanged. Control experiments showed that 10-Hz rTMS delivered at subthreshold intensity also increased the ISP. rTMS over the hand motor area did not facilitate ISPs in the biceps muscles. Finally, rTMS-induced ISP facilitation did not outlast the 10-Hz rTMS train. These findings suggest that rTMS at a frequency of 10 Hz potentiates the interhemispheric inhibitory mechanisms responsible for the ISP, partly through temporal summation. The distinct changes in the ISP and CSP suggest that rTMS facilitates intrahemispheric and interhemispheric inhibitory phenomena through separate neural mechanisms. The ISP facilitation induced by high-frequency rTMS is a novel, promising tool to investigate pathophysiological abnormal interhemispheric inhibitory transfer in various neurological diseases.

Physical interactions between induced electrical fields can have substantial effects on neuronal excitation during simultaneous TMS of two brain areas.

OBJECTIVE: To analyse the interactions between simultaneous or nearly simultaneous focal transcranial magnetic stimulation (TMS) of the motor cortex hand area (M1hand) of both hemispheres. METHODS: In 7 healthy subjects, motor evoked potential (MEP) amplitude and cortical silent period (CSP) duration were elicited in the right hand by bihemispheric focal TMS of M1hand (8-shaped coils, monophasic current waveform, stimulus intensity 120% above motor threshold, TMS of right M1hand preceding TMS of left M1hand by 0-1000 micros), or by unilateral TMS of left M1hand alone. A dipole probe was used to measure the physical interactions between the two stimulating coils. RESULTS: Bihemispheric TMS markedly decreased MEP and CSP at intervals of 0 and 50 micros compared to unilateral TMS, whereas both measures increased at the interval of 150 micros. The dipole probe experiments showed that the physical interactions between the electrical fields of the two coils entirely explained the MEP and CSP findings, but only under the assumption that excitation of M1hand is not point-focal but extends over several centimetres. CONCLUSIONS: First, simultaneous focal TMS of distant brain sites may result in marked 'distortion' of brain excitation through physical interaction between the induced electrical fields. Second, these findings support the notion that excitation of human M1hand is relatively non-focal, even if a 'focal' stimulating coil and low stimulus intensity are used. SIGNIFICANCE: Potentially marked physical interaction between induced electrical fields must be taken into account when testing or disrupting distant brain sites with simultaneous focal TMS.

Adverse motor effects induced by antiepileptic drugs.

Cognitive effects of anti-epileptic drugs (AEDs) have been already extensively reported. In contrast, motor disturbances, frequently induced by these drugs, have not received similar attention. We review subjective and objective adverse motor effects of traditional and new AEDs. We discuss the methodological issues caused by the heterogeneous sources of information on drug adverse effects (controlled clinical studies, open studies, and case reports). We describe specific disturbances (vestibulocerebellar, dyskinesias, parkinsonism, tics, myoclonus, and tremor) as the effects of different AEDs on distinct motor circuitries. Finally, we summarize the role of sophisticated technical studies which provide a valuable insight into the specific or subtle effects of AEDs on the central nervous system.

Suprathreshold 0.3 Hz repetitive TMS prolongs the cortical silent period: potential implications for therapeutic trials in epilepsy.

OBJECTIVE: To investigate the after-effects of 0.3 Hz repetitive transcranial magnetic stimulation (rTMS) on excitatory and inhibitory mechanisms at the primary motor cortex level, as tested by single-pulse TMS variables. METHODS: In 9 healthy subjects, we studied a wide set of neurophysiological and behavioral variables from the first dorsal interosseous before (Baseline), immediately after (Post 1), and 90 min after (Post 2) the end of a 30 min long train of 0.3 Hz rTMS delivered at an intensity of 115% resting motor threshold (RMT). Variables under investigation were: maximal M wave, F wave, and peripheral silent period after ulnar nerve stimulation; RMT, amplitude and stimulus-response curve of the motor evoked potential (MEP), and cortical silent period (CSP) following TMS; finger-tapping speed. RESULTS: The CSP was consistently lengthened at both Post 1 and Post 2 compared with Baseline. The other variables did not change significantly. CONCLUSIONS: These findings suggest that suprathreshold 0.3 Hz rTMS produces a relatively long-lasting enhancement of the inhibitory mechanisms responsible for the CSP. These effects differ from those, previously reported, of 0.9-1 Hz rTMS, which reduces the excitability of the circuits underlying the MEP and does not affect the CSP. This provides rationale for sham-controlled trials aiming to assess the therapeutic potential of 0.3 Hz rTMS in epilepsy.

Congenital hemiparesis: different functional reorganization of somatosensory and motor pathways.

OBJECTIVES: To investigate the reorganization of somatosensory and motor cortex in congenital brain injury. METHODS: We recorded motor evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) and somatosensory evoked potentials (SEPs) in a 41 year old man with severe congenital right hemiparesis but only mild proprioceptive impairment. Brain magnetic resonance imaging showed a large porencephalic cavitation in the left hemisphere mainly involving the frontal and parietal lobes. RESULTS: TMS showed fast-conducting projections from the undamaged primary motor cortex to both hands, whereas MEPs were not elicited from the damaged hemisphere. Left median nerve stimulation evoked normal short-latency SEPs in the contralateral undamaged somatosensory cortex. Right median nerve stimulation did not evoke any SEP in the contralateral damaged hemisphere, but a middle-latency SEP (positive-negative-positive, 39-44-48 ms) in the ipsilateral undamaged hemisphere, with a fronto-central scalp distribution. CONCLUSIONS: Our data show that somatosensory function of the affected arm is preserved, most likely through slow-conducting non-lemniscal connections between the affected arm and ipsilateral non-primary somatosensory cortex. In contrast, motor function was poor despite fast-conducting ipsilateral cortico-motoneuronal output from the primary motor cortex of the undamaged hemisphere to the affected arm. This suggests that different forms of reorganization operate in congenital brain injury and that fast-conducting connections between primary cortex areas and ipsilateral spinal cord are not sufficient for preservation or recovery of function.

Bilateral motor cortex output with intended unimanual contraction in congenital mirror movements.

In congenital mirror movements (MM), it is unclear whether the "mirror" motor cortex (M1) produces output during intended unimanual movements. In two patients with MM, the cortical silent period (CSP) was abnormally short after focal transcranial magnetic stimulation (TMS) of either M1, but simultaneous bilateral TMS led to significant CSP lengthening. Thus, it is likely that the shortened CSP after unilateral TMS is caused by output from the nonstimulated M1, suggesting that both M1 produce output with intended unimanual movements in patients with MM.

Cortical silent period in two patients with meningioma and preoperative seizures: a pre- and postsurgical follow-up study.

OBJECTIVES: Prolongation of the cortical silent period (CSP) following transcranial magnetic stimulation has been reported in patients with partial epilepsy involving the primary motor cortex (M1). This study aimed to investigate the relationship between the expected intraindividual variations in risk factors for seizures and CSP duration. METHODS: We studied a 59-year-old woman with a rolandic meningioma and simple motor partial seizures and a 71-year-old woman with a parietal/occipital meningioma and complex partial seizures. Both patients had seizure as their initial symptom with complete postsurgical remission. Repeated pre- and postoperative CSP recordings were made from both first dorsal interosseous muscles. We compared the results to those obtained in 13 normals. RESULTS: In the patient with simple motor partial seizures, the CSP was significantly prolonged in preoperative recordings and 3 weeks after surgery. This CSP lengthening partly subsided 3 months after surgery. Finally, the CSP was normal 6, 8, and 18 months after surgery. In the patient with complex partial seizures, no CSP change was observed. CONCLUSIONS: In our patient with a rolandic meningioma, CSP prolongation was observed when the risk of seizure relapse was supposed to be higher (preoperative and early postoperative periods). This supports the view that CSP changes reflect compensatory mechanisms in M1 epilepsy.

Reorganization of the motor cortex in a patient with congenital hemiparesis and mirror movements.

Abnormal branching of corticospinal fibers from the unaffected motor cortex is responsible for mirror movements in patients with congenital hemiparesis, but it is unknown which mechanisms enable these patients to lateralize motor activity. Using multiunit electromyographic analysis and transcranial magnetic stimulation, the authors provide evidence for nonbranched crossed and uncrossed corticospinal projections and intracortical inhibition of the mirror hand. They propose that this remarkable reorganization of the unaffected motor cortex helps these patients to reduce mirror movements.

Remote effects of cortical dysgenesis on the primary motor cortex: evidence from the silent period following transcranial magnetic stimulation.

OBJECTIVE: In cortical dysgenesis (CD), animal studies suggested abnormal cortico-cortical connections. Cerebral areas projecting to the primary motor cortex (M1) modulate the cortical silent period (CSP) following transcranial magnetic stimulation (TMS). Therefore, we used the CSP to investigate remote effects of CD on the M1. METHODS: A detailed investigation, including single-pulse TMS and electrical nerve stimulation, was performed in 3 consecutive adults with focal CD located outside the M1 and in 18 controls. Two patients with unilateral CD were epileptic and treated with anti-epileptic drugs. One patient with focal CD on both sides had no history of seizures. Neurological examination was normal in all patients. Recordings were made from both first dorsal interosseous muscles. RESULTS: In CD patients, the CSP was significantly lengthened contralaterally to the affected hemispheres. In treated patients with unilateral CD, the interside difference of the CSP duration was also significantly increased. In contrast, excitability threshold, peripheral and corticospinal motor conduction studies, and peripheral as well as ipsilateral silent periods were not significantly modified. CONCLUSIONS: Our findings indicate that focal CD outside the M1 may produce CSP modifications, which are likely due to changes of afferent control.

Dissociation of the pathways mediating ipsilateral and contralateral motor-evoked potentials in human hand and arm muscles.

1. Growing evidence points toward involvement of the human motor cortex in the control of the ipsilateral hand. We used focal transcranial magnetic stimulation (TMS) to examine the pathways of these ipsilateral motor effects. 2. Ipsilateral motor-evoked potentials (MEPs) were obtained in hand and arm muscles of all 10 healthy adult subjects tested. They occurred in the finger and wrist extensors and the biceps, but no response or inhibitory responses were observed in the opponens pollicis, finger and wrist flexors and the triceps. 3. The production of ipsilateral MEPs required contraction of the target muscle. The threshold TMS intensity for ipsilateral MEPs was on average 1.8 times higher, and the onset was 5.7 ms later (in the wrist extensor muscles) compared with size-matched contralateral MEPs. 4. The corticofugal pathways of ipsilateral and contralateral MEPs could be dissociated through differences in cortical map location and preferred stimulating current direction. 5. Both ipsi- and contralateral MEPs in the wrist extensors increased with lateral head rotation toward, and decreased with head rotation away from, the side of the TMS, suggesting a privileged input of the asymmetrical tonic neck reflex to the pathway of the ipsilateral MEP. 6. Large ipsilateral MEPs were obtained in a patient with complete agenesis of the corpus callosum. 7. The dissociation of the pathways for ipsilateral and contralateral MEPs indicates that corticofugal motor fibres other than the fast-conducting crossed corticomotoneuronal system can be activated by TMS. Our data suggest an ipsilateral oligosynaptic pathway, such as a corticoreticulospinal or a corticopropriospinal projection as the route for the ipsilateral MEP. Other pathways, such as branching of corticomotoneuronal axons, a transcallosal projection or a slow-conducting monosynaptic ipsilateral pathway are very unlikely or can be excluded.

Motor imagery in a locked-in patient: evidence from transcranial magnetic stimulation.

Motor evoked potentials (MEPs) to transcranial magnetic stimulation were evaluated in a case of locked-in syndrome due to a large pontine infarction. In this patient, magnetic resonance imaging (MRI) and somatosensory evoked potentials demonstrated a tegmental involvement. One month after the attack, no MEP could be recorded from the right abductor digiti minimi (ADM) or either tibialis anterior muscle. On the contrary, MEPs were obtained from the left ADM, although with a prolonged latency and a reduced amplitude. When the patient was requested to think about the abduction of her paralyzed left little finger, the latency and the elicitability of these responses improved as compared with the relaxed condition. These severe MEP alterations correctly predicted a poor recovery of motor function in the chronic stage. However, although the tegmental involvement raises the question of an insufficient cortical motor arousal, preserved motor imagery suggested a normal cortical motor area activation.

Interictal inhibitory mechanisms in patients with cryptogenic motor cortex epilepsy: a study of the silent period following transcranial magnetic stimulation.

The silent period (SP) following transcranial magnetic stimulation (TMS) of the motor cortex is mainly due to cortical inhibitory mechanisms. The aim of the present study was to investigate these inhibitory phenomena in primary motor cortex epilepsy. We studied the TMS-induced SP in both the first dorsal interosseous (FDI) muscles in 8 patients who suffered from cryptogenic partial epilepsy with seizures starting with clonic movements of the right upper limb. All patients were on chronic medication with antiepileptic drugs. Therefore, besides contrasting the results with 16 age-matched normal controls, we also studied 10 patients receiving similar antiepileptic treatments who suffered from cryptogenic partial epilepsy with seizures characterised by the absence of clonic manifestations. The duration of the SP was bilaterally increased in the patients with clonic seizures when compared with the two other groups of subjects. The SP was longer in the left FDI muscle (contralateral to the side of the clonic manifestation in all the patients). Our findings likely indicate enhanced interictal inhibitory mechanisms in patients with partial epilepsy involving the primary motor cortex. The resulting inhibitory effect could be greater in the intact hemisphere rather than in the affected one, in which the hyperexcitability of the epileptic focus had to be counterbalanced.