Contrast-enhanced transcranial Doppler for the detection of right-to-left shunt: A new provocation method with a syringe-modified Valsalva maneuver.

BACKGROUND: Contrast-enhanced transcranial Doppler (cTCD) study has been established as one of the most common investigations for detecting right-to-left shunt (RLS). Although the conventional Valsalva maneuver (c-VM) has been used to increase the sensitivity of cTCD for RLS, efforts are still needed to improve the detection rate further. We proposed a new provocation method with a syringe-modified Valsalva maneuver (sm-VM) during cTCD and compared the efficacy of this strategy with cTCD measured at resting and with the provocation of c-VM. METHODS: Consecutive patients with suspicion of RLS who underwent cTCD in our institution between September 27, 2021, and April 1, 2022, were included in this study. Examination of cTCD was performed separately at the resting state and provoked with c-VM and sm-VM. The overall proportion of patients with RLS and their distribution with different RLS grades were compared. RESULTS: A total of 389 patients (mean age: 49.37 years, male: 52.2%) were included in this study. The positive rate for RLS was significantly higher for cTCD detected with sm-VM than those detected at resting state and with c-VM (46.8% vs. 21.6% and 34.2%, all p < .05). Besides, cTCD detected with sm-VM was also associated with a higher proportion of patients with grade III RLS than those detected at resting state and with c-VM (11.3% vs. 1.8% and 0%, all p < .05). CONCLUSIONS: Compared to cTCD detected at resting state and with c-VM, cTCD with sm-VM could further increase the positive detection rate of RLS.

Agitated saline with 10% blood increases number and stability of microbubbles in detection right-to-left shunt by contrast-enhanced transcranial Doppler: an in vitro and in vivo observational study.

Background: Agitated saline (AS) with blood has been shown to have good tolerance and increased efficacy when used in contrast-enhanced transcranial Doppler (c-TCD) to detect right-to-left shunt (RLS). However, little is known about the effects of blood volume on c-TCD results. Our study investigated the characterization of AS with different blood volumes in vitro and compared the c-TCD results in vivo. Methods: In vitro, AS without blood, AS with 5% blood (5% BAS), and AS with 10% blood (10% BAS) were prepared based on previous studies and observed under microscopy. The numbers and sizes of the microbubbles from different contrast agents were compared immediately, 5 min, and 10 min post-agitation. In vivo, 74 patients were recruited. c-TCD was repeated 3 times using AS with different blood volumes in each patient. Signal detection times, positive rates, and classifications of RLS were compared among the 3 groups. Results: In vitro, the AS without blood produced 5.4±2.4/field microbubbles after agitation, the 5% BAS produced 30.4±4.2/field, and the 10% BAS produced 43.9±12.7/field. More microbubbles remained in the 10% BAS than the 5% BAS within 10 min (18.5±6.1 vs. 7.1±2.0/field, P<0.001). The size of the microbubbles from the 5% BAS increased from 9.2±8.2 to 22.1±10.6 µm within 10 min post-agitation (P=0.014), while the 10% BAS changed insignificantly. In vivo, the signal detection times of the 5% BAS (1.1±0.7 s) and 10% BAS (1.0±0.8 s) were significantly shorter than the AS without blood (4.0±1.5 s, P<0.0001). The RLS positive rates were 63.5%, 67.6% and 71.6% in AS without blood, 5% BAS and 10% BAS respectively; however, the differences were not statistically significant. The AS without blood reached 12.2% level III RLS, while the 5% BAS reached 25.7%, and the 10% BAS reached 35.1% (P=0.005). Conclusions: The 10% BAS would be suggested in c-TCD as it addressed larger RLS by increasing the number and stability of microbubbles, and it improves the diagnosis of patent foramen ovale (PFO).

Effect of Interventional Therapy Unexplained Dizziness and Relationship Between Dizziness Handicap Inventory and Right-to-Left Shunt Grading.

Objective: Unexplained dizziness remains a clinical challenge. Our previous studies have shown that unexplained dizziness may be related to patent foramen ovale (PFO). This study aims to explore whether the degree of shunt is correlated with the degree of unexplained dizziness and looking for the possible clinical intervention for patients with unexplained dizziness. Methods: This study was a large single-center, prospective, controlled study. From March 2019 to March 2022, patients with unexplained dizziness and explained dizziness and healthy controls were recruited. Contrast-enhanced transcranial Doppler sonography (c-TCD) was performed to detect the existence of right-to-left shunt (RLS) and shunt grading. The dizziness handicap inventory (DHI) was completed to evaluate the dizziness. Unexplained dizziness patients with large amount of PFO were volunteered to receive medication treatment and transcatheter PFO closure and followed up six months. Results: A total of 387 patients (132 unexplained, 123 explained and 132 controls) were enrolled. There was a statistical difference in the RLS grading with three groups (p < 0.001). The Spearman correlation coefficient of RLS grading and DHI scores in unexplained dizziness patients (r=0.122, p=0.163) and explained dizziness patients (r=0.067, p=0.460). In the unexplained group, there were 49 cases with massive grading RLS. Of which 25 patients received percutaneous PFO closure treatment and 24 cases received medication treatment. Followed up six months after treatment, the amount of DHI scores change in patients who received the percutaneous PFO closure was significantly higher than that in the medication treatment group (p < 0.001). Conclusion: RLS may play an important role in unexplained dizziness. For unexplained dizziness patients, PFO closure may contribute to better outcomes. In the future, large-scale randomized controlled studies are still needed.

Contrast-enhanced transcranial doppler versus contrast transthoracic echocardiography for right-to-left shunt diagnosis.

RLS can be diagnosed using US, CT angiography, and right heart catheterization. However, most reliable diagnostic modality remains undetermined. c-TCD was more sensitive than c-TTE in the diagnosis of RLS. This was true especially for the detection of provoked shunts or mild shunts. c-TCD can be used as the preferred screening method for RLS.

The Relationship Between Patent Foramen Ovale and Unexplained Dizziness: A Prospective Analysis in China.

Introduction: Patent foramen ovale (PFO) is potentially associated with abnormal embolisms, and it results in mixing of arteriovenous blood when its right-to-left shunt (RLS) emerges. Present studies have found that PFO is a risk factor that can lead to many diseases. However, few studies have examined the relationship between PFO and dizziness. Methods: This study was a large single-center, prospective, controlled study. From March 2019 to March 2021, we recruited patients with dizziness were divided into two groups: "explained" and "unexplained". All patients were submitted to contrast-enhanced transcranial Doppler ultrasound and screened for PFO. Transesophageal heart ultrasound or right heart catheterization was used to confirm PFO. Additionally, multiple factors were collected and statistical analysis was performed between the two groups. Results: Among the 244 patients included, 123 were in the "explained" group and 121 were in the "unexplained" group. The prevalence of PFO in the "explained" group was 34 (27.4%) compared to 79 (64.7%) in the "unexplained" group. In the "explained" group, 7 were RLS level IV, 6 were level III, 7 were level II, and 14 were level I. For the "unexplained" group, the numbers of patients with levels IV, III, II and I were 27, 26, 12 and 14, respectively. Univariate analysis revealed that PFO (χ2= 34.77, P < 0.001) and age (t = -3.49, P < 0.001) seemed to be potential risk factor candidates for "unexplained" dizziness. In multiple regression analysis, age (OR = 0.97; 95% CI 0.95-0.99) and the prevalence of PFO (OR = 4.37; 95% CI 2.50-7.63) were statistically significant. Massively shunted PFO showed more pronounced risk factors (OR = 8.76; 95% CI 4.04-19.03). Conclusion: There was a high prevalence of PFO and a greater RLS level in unexplained dizziness. PFO and age were independent risk factors for unexplained dizziness. When treating with unexplained dizziness, especially among young people, we must pay attention to the presence of PFO.

Evaluation of right-to-left shunt on contrast-enhanced transcranial Doppler in patent foramen ovale-related cryptogenic stroke: Research based on imaging.

BACKGROUND: Cardiogenic embolism caused by patent foramen ovale (PFO) is a common etiology of cryptogenic stroke (CS), particularly in young and middle-aged patients. Studies about right-to-left shunt (RLS) detection using contrast-enhanced transcranial Doppler (c-TCD) are numerous. According to the time phase and number of microbubbles detected on c-TCD, RLS can be classified and graded. We hypothesized that the characteristics of an infarction lesion on diffusion-weighted imaging differs when combining the type and grade of RLS on c-TCD in patients with PFO-related CS. AIM: To explore the characteristics of infarction lesions on diffusion-weighted imaging when combining the RLS type and grade determined by c-TCD. METHODS: We retrospectively evaluated CS patients from August 2015 to December 2019 at a tertiary hospital. In total, 111 PFO-related CS patients were divided according to whether RLS was permanent (microbubbles detected both at resting state and after the Valsalva maneuver) or latent (microbubbles detected only after the Valsalva maneuver) on c-TCD. Each group was subdivided into small, mild and large RLS according to the grade of shunt on c-TCD. A normal control group was composed of 33 patients who suffered from simple dizziness. Intragroup and intergroup differences were analyzed in terms of clinical, laboratory and diffusion-weighted imaging lesion characteristics. The correlation between RLS grade evaluated by c-TCD and size of PFO determined by transesophageal echocardiography were also analyzed. RESULTS: In 111 patients with PFO-related CS, 68 had permanent RLS and 43 had latent RLS. Clinical characteristics and laboratory tests were not significantly different among the permanent RLS, latent RLS and normal control groups. The proportion of patients with multiple territory lesions in the permanent RLS group (50%) was larger than that in the latent RLS group (27.91%; P = 0.021). Posterior circulation was more likely to be affected in the latent RLS group than in the permanent RLS group (30.23% vs 8.82%, P = 0.004). Permanent-large and latent-large RLS were both more likely to be related to multiple (P trend = 0.017 and 0.009, respectively), small (P trend = 0.035 and 0.006, respectively) and cortical (P trend = 0.031 and 0.033, respectively) lesions. The grade of RLS evaluated by c-TCD was correlated to the size of PFO determined by transesophageal echocardiography (r = 0.758, P < 0.001). CONCLUSION: Distribution of the infarct suggested the possible type of RLS. Multiple, small and cortical infarcts suggest large RLS induced by a large PFO.

Relevance of small right-to-left shunt in contrast-enhanced transcranial Doppler in young and middle-aged patients with cryptogenic stroke: a report of two cases and literature review.

AIM: The clinical relevance of small right-to-left shunt (RLS) in young patients with cryptogenic stroke is unknown. We aimed to analyze and understand the relationship between cryptogenic stroke and small RLS by studying specific cases. MATERIALS AND METHODS: Clinical data from two cases of small RLS-related cryptogenic stroke in young patients were collected prospectively and analyzed. We followed up the patients for >1 year after discharge. RESULTS: Case 1. A 50-year-old man was admitted for slurred speech and right hemiplegia and was diagnosed with acute cerebral infarction. Contrast-enhanced transcranial Doppler (c-TCD) and contrast-enhanced transthoracic echocardiography (c-TTE) revealed a microbubble and 20-30 microbubbles per section, respectively, in the resting state. Three months later, he was readmitted for stroke recurrence. Transesophageal echocardiography (TEE) confirmed a patent foramen ovale (PFO), and he underwent transcatheter closure of the PFO. Case 2. A 48-year-old man was admitted for right hemiplegia with slurred speech. Brain magnetic resonance imaging showed acute cerebral infarction. c-TCD and contrast-enhanced TEE (c-TEE) revealed <10 microbubbles and approximately 20 microbubbles per section, respectively. These findings suggested a PFO. Two months later, he was readmitted for stroke recurrence. He underwent transcatheter closure of the PFO. Follow-up of cases 1 and 2 at >1 and >1.5 years after discharge, respectively, showed no stroke recurrence. CONCLUSION: We suspected that a small RLS may cause cryptogenic stroke. A small RLS in c-TCD in stroke patients may not be actually small, and c-TEE/c-TTE may be valuable in finding larger RLSs.

The relation of cryptogenic ischemic stroke and migraine with aura patients with different right-to-left shunt volume by contrast enhanced transcranial Doppler / 中风与神经疾病杂志

@#Objective　To investigate the feature of the shunt volume of right-to-left shunt (RLS) in cryptogenic ischemic stroke (CIS) and migraine with aura (MA) and to analyze the different pathogenesis of CIS and MA with RLS.Methods　Forty-eight CIS patients and 42 MA patients from two case groups and 33 healthy volunteers from normal control group(NCG),using contrast enhanced transcranial doppler (cTCD) for diagnosing RLS and shunt volume grades,the positive rate of the three groups were analyzed.Results　In the case groups，the positive rate of RLS was MA 57.1% (24/42) and CIS 60.4%(29/48),of which large shunt accounted for MA 16.7% (7/42) and CIS 29.2%(14/48).In the NCG,the positive rate of RLS was 30.3% (10/33),of which large shunt accounted for 9.1% (3/33).Comparison of the three groups of the total positive rate，the total positive rate of two case groups were higher than NCG (MA vs NCG,P=0.02),(CIS vs NCG,P=0.008).Large shunt rate in CIS group was significantly higher than NCG (P=0.029).Conclusion　CIS and MA are significantly related to RLS.The large shunt rate of RLS in CIS patients was significantly higher than that in NCG.

Is inferior vena cava compression an alternative for valsalva maneuver in contrast-enhanced transcranial doppler？.

OBJECTIVES: To evaluate whether inferior vena cava compression (IVCC) can be an alternative for valsalva maneuver (VM) in contrast-enhanced transcranial doppler (c-TCD). METHODS: Patients diagnosed with ischemic stroke, transient ischemic attack, and migraine were enrolled in this study. C-TCD was conducted at resting state, after VM and IVCC to detect right to left shunt (RLS). Then, the RLS was compared to examine whether IVCC could be an alternative for VM in c-TCD. RESULTS: A total of 246 patients were enrolled in this study. Via Wilcoxon signed-rank test of paired data, the detection for RLS of c-TCD conducted after IVCC was superior to at resting state, but inferior to after VM (P ï¼œ .001, P = .01, respectively); the detection for RLS of c-TCD conducted after IVCC was inferior to after VM for patients with good cooperation of VM, but was superior for patients with poor cooperation of VM (P ï¼œ .001, P ï¼œ .001, respectively); the detection for RLS of c-TCD conducted after IVCC and after VM showed no significant difference for patients with good cooperation of VM and without abdominal obesity, or with poor cooperation of VM and with abdominal obesity (P = .201, P = .157, respectively); the detection for RLS of c-TCD conducted after IVCC was superior to at resting state for patients with abdominal obesity (P ï¼œ .001). CONCLUSIONS: For patients with poor cooperation of VM, IVCC could be used as an effective supplement to increase the detection of RLS in c-TCD.

A single center study on the correlation between Cryptogenic stroke and right-to-left shunt by contrast enhanced transcranial doppler in Liaoning province / 中风与神经疾病杂志

@#Objective　To investigate the prevalence of right-to-left shunt（RLS） in cryptogenic stroke patients and analyze the relationship between cryptogenic stroke and RLS. Methods　We enrolled 44 cryptogenic stroke patients between 18-55 years old as case grope and 33 healthy volunteers as control group，using contrast enhanced transcranial doppler（cTCD） and contrast transthoracic echocardiography（cTTE） for diagnosis of RLS and grade，the positive rate of the two groups were statistically analyzed. Results　In the case group，the positive rate of RLS was 47.7%（21 /44），of which large shunt accounted for 27.3%（12/44）. In the control group，the positive rate of RLS was 30.3%（10 /33），of which large shunt accounted for 9%（3/33）. Comparison of two groups of the total positive rate，the total positive rate of case group was same to the control group，there was not statistically significant difference（χ2=2.380，P=0.123） ．Large shunt rate in case group was significantly higher than the control group（χ2=3.974，P=0.042）. Conclusion　cTCD is a responsible approach to diagnose RLS. Cryptogenic stroke is related to RLS，and the large shunt may be the important cause of cryptogenic stroke，which should be paid more attention to.

Correlation between RoPE score and right-to-left shunt severity in patients with cryptogenic stroke / 西安交通大学学报(医学版)

Objective To compare the clinical features between cryptogenic stoke(CS)with and without right-to-left shunt(RLS)so as to determine whether shunt severity determined by control-enhanced transcranial Doppler(c-TCD)is correlated with the risk of paradoxical embolism(RoPE)score.Methods We made a retrospective analysis of clinical characteristics of 138 CS patients with and without RLS admitted to our department between January 2014 and November 2016.For patients documented by c-TCD,we evaluated whether there was a correlation between RLS severity and RoPE score. RLS was diagnosed by c-TCD and contrast-enhanced transthoracic echocardiography(c-TTE).We compared every modality for detecting RLS with and without Valsalva maneuver.For patients found with RLS in c-TCD and c-TTE,we judged whether there was an agreement in grading RLS between two modalities.Results For patients with CS,shunt severity by c-TCD was positively correlated with RoPE score(r= 0.26,P= 0.05).The clinical features were different between CS patients with RLS and without RLS.Compared with the positive results of c-TCD and c-TTE at rest,the positive rate was higher in Valsalva maneuver,respectively(P＜0.01).There was a moderate agreement between shunt grades identified by the two techniques(Kappa=0.428).Conclusion There is a positive correlation between RoPE score and RLS severity determined by c-TCD in CS patients.Valsalva maneuver can significantly increase the positive rate of RLS detected by c-TCD and c-TTE.

Clinical characteristics of patients with cryptogenic stroke and patent foramen ovale / 第二军医大学学报

Objective To investigate the clinical characteristics of patients with cryptogenic stroke and patent foramen ovale (PFO). Methods The clinical features, imaging findings and therapeutic outcomes of 51 patients with cryptogenic stroke and PFO, who received treatment in Stroke Center of Changhai Hospital of Navy Medical University (Second Military Medical University) between Sep. 2013 and Jan. 2018, were retrospectively analyzed. Results Of the 51 cases, 41 were male and 10 were female; and the mean age was (53.92±14.83) years (ranging from 21 to 84 years). Diffusion weighted imaging (DWI) showed that 46 patients developed new infarction including 20 cases (43.5%) of single lesion and 26 cases (56.5%) of multiple lesions, of which 15 cases (57.7%) involved single arterial territory and 11 cases (42.3%) involved two or more arterial territories (4 cases of bilateral anterior circulation, and 7 cases of both the anterior and posterior circulations). Thirty-seven patients underwent contrast-enhanced transcranial Doppler (cTCD) examination, which showed that 31 cases (83.8%) had microbubble sign (air microbubble emboli of 4 cases looked like raindrops or curtains). In 50 patients undergoing transesophageal echocardiography (TEE) examination, 49 cases (98.0%) were accompanied with PFO. Nine patients received intravenous thrombolysis. In secondary prevention, 18 patients received single antiplatelet therapy, 12 dual antiplatelet therapy, 8 anticoagulation therapy, and 13 PFO closure+single antiplatelet therapy. One patient with single antiplatelet therapy had recurrent ischemic stroke, 2 patients with dual antiplatelet therapy had recurrent ischemic stroke, and the patients with percutaneous closure of PFO had no recurrent stroke. Conclusion The infarction of cryptogenic stroke with PFO involves single or multiple arterial territories, cTCD and TEE have high positive diagnosis rate for PFO, and the patients with selective antithrombotic therapy and PFO closure have a low risk of recurrent stroke.

Comparison of Different Methods of Valsalva Maneuver for Right-to-left Shunt Detection by Contrast-Enhanced Transcranial Doppler.

We evaluated 298 patients for right-to-left shunt (RLS) detection by contrast-enhanced transcranial Doppler at rest state (RS), during the conventional Valsalva maneuver (CM), and during the modified Valsalva maneuver (BM: blowing into the connecting tube of a sphygmomanometer at 40 mm Hg for 10 s) in random order, and the degree of RLS along the time of the first microbubble occurrence was recorded. The positive rates were 21.8%, 36.9% and 47.3% for RS, CM and BM, respectively (p < 0.001). BM resulted in a significantly higher positive rate (p = 0.010), and there was a significant difference between the two different methods of VM in terms of the degree of RLS detection (p < 0.001). Further, the first microbubble occurred later during BM than CM (10.22 ± 3.77 s vs. 9.44 ± 4.36 s, p < 0.05). This modified maneuver is an alternative to the conventional one, especially for those who cannot perform the conventional maneuver adequately, but are highly suspected of having RLS.

[Detection of an intrapulmonary shunt in patients with liver cirrhosis through contrast-enhanced transcranial Doppler. A study of prevalence, pattern characterization, and diagnostic validity]. / Detección del shunt intrapulmonar en pacientes con cirrosis hepática mediante doppler transcraneal con contraste. Estudio de prevalencia, caracterización del patrón y validez diagnóstica.

INTRODUCTION: Intrapulmonary vascular dilatations (IPVD) are considered a complication of cirrhosis. The technique of choice for their diagnosis is contrast-enhanced echocardiography (CEE). The aim of this study was to determine the usefulness of contrast-enhanced transcranial Doppler (CETD) in the diagnosis of IPVD. METHOD: We consecutively included patients evaluated for liver transplantation. A cross-sectional study was conducted. The investigator interpreting CETD was blind to the results of the gold standard (CEE). The accuracy of the diagnostic test was evaluated through sensitivity, specificity, positive and negative predictive values, and likelihood ratio. RESULTS: CETD (n=43) showed a right-to-left shunt in 23 patients (62.2%): 4 early, 2 indeterminate and 17 late. Nineteen (51,4%) cases were classified as IPVD. With CEE (n=37), 10 procedures (27%) were negative for shunt, 27 (73%) were positive, and 21 (56.8%) were compatible with IPVD. Patients with and without IPVD showed no differences in age, sex, etiology, severity, or MELD score, independently of the diagnostic test. In the diagnostic validity study (n=37) of CETD versus CEE, the AUC for diagnostic yield was 0.813% (95%CI: 0.666-0.959; P=.001), sensitivity was 76.2% (95%CI: 54.9-89.4) and specificity was 90% (95%CI: 63.9-96.5). The positive likelihood ratio was 6.095. CONCLUSIONS: We found a high prevalence of IPVD in candidates for liver transplantation. When a late right-to-left shunt with recirculation is observed, CETD has a high probability of detecting IPVD, with few false-positive results. Because this technique has not previously been described in this indication, similar studies are needed for comparison.

Effects of patient position on right-to-left shunt detection by contrast transcranial Doppler.

Contrast-enhanced transcranial Doppler (c-TCD) was performed on 117 patients to detect a right-to-left shunt (RLS). Each patient was examined during normal breathing and after performing the Valsalva maneuver (VM) in three randomly ordered positions: supine, left lateral decubitus and sitting upright. When breathing normally, RLS-positive rates were 15.4%, 23.1% and 28.2% for supine, left lateral decubitus and upright sitting positions, respectively. After VM, the positive rates were 25.6%, 28.2% and 36.8%, respectively. For each position, the RLS-positive rates were higher after VM than normal breathing and higher for the left lateral decubitus and upright sitting positions compared with the supine position, irrespective of breathing. There were no significant differences between findings for the left lateral decubitus and upright sitting positions. No significant differences in shunt grades were found across all groups. The choice of position for patients undergoing c-TCD can improve its sensitivity for the diagnosis of RLS.

Comparison of Contrast-enhanced Transcranial Doppler with Transesophageal Echocardiography in Patent Foramen Ovale Detectionin Acute Cerebral Ischemic Patients / 中国康复理论与实践

@# Objective To evaluate the effect of contrast-enhanced transcranial Doppler (c-TCD) for detection of patent foramen ovale (PFO) comparing to transesophageal echocardiography (TEE). Methods 28 ischemic stroke patients with PFO detected with TEE were evaluated with TCD bubble study at rest and under Valsalva maneuver (VM). Results PFO was identified in 20 cases (71.43%) at rest by TCD bubble study. When VM was performed, PFO was detected in 24 cases (85.71%). There was no relevant in sensitivity of c-TCD with PFO size (P>0.05). Conclusion c-TCD is an excellent method for PFO identification with high sensibility while under VM. C-TCD can be used as a screening method for suspected PFO in patients with stroke test before TEE.