Implementación de la disección endoscópica submucosa esofágica en España: resultados del registro nacional / Implementation of esophageal endoscopic submucosal dissection in Spain: Results from the nationwide registry

Introducción y objetivos Los resultados de la disección submucosa endoscópica (DSE) en el esófago no han sido evaluados en nuestro país. Nuestro objetivo principal fue analizar la efectividad y la seguridad de la técnica. Material y métodos Análisis del registro nacional prospectivo de DSE. Se incluyeron todas las lesiones superficiales esofágicas extirpadas mediante DSE en 17 hospitales (20 endoscopistas) entre enero de 2016 y diciembre de 2021. Se excluyeron las lesiones subepiteliales. La variable principal fue el porcentaje de resección curativa. Se realizó un análisis de regresión logística para conocer los predictores de resección no curativa y un análisis de supervivencia. Resultados Se realizaron un total de 102 DSE en 96 pacientes. El éxito técnico fue del 100% y el porcentaje de resección en bloque, del 98%. El porcentaje de resección R0 y curativa fue del 77,5% (n = 79; IC 95%: 68%-84%) y del 63,7% (n = 65; IC 95%: 54%-72%), respectivamente. La histología más frecuente fue la neoplasia sobre esófago de Barrett (n = 55 [53,9%]). El principal motivo de resección no curativa fue la invasión submucosa profunda (n = 25). Los centros con menor volumen de casos obtuvieron cifras inferiores de resección curativa. El porcentaje de perforación, sangrado diferido y estenosis posprocedimiento fue del 5%, del 5% y del 15,7%, respectivamente. Ningún paciente falleció ni requirió cirugía por un efecto adverso. Tras una mediana de seguimiento de 14 meses, 20 pacientes (20,8%) recibieron cirugía y/o quimio-radioterapia, y 9 fallecieron (mortalidad del 9,4%). Conclusiones En nuestro medio, la DSE esofágica es curativa en aproximadamente dos de cada tres pacientes, con un riesgo aceptable de efectos adversos (AU)

Introduction and aims The outcomes of endoscopic submucosal dissection (ESD) in the esophagus have not been assessed in our country. Our primary aim was to analyze the effectiveness and safety of the technique. Material and methods Analysis of the prospectively maintained national registry of ESD. We included all superficial esophageal lesions removed by ESD in 17 hospitals (20 endoscopists) between January 2016 and December 2021. Subepithelial lesions were excluded. The primary outcome was curative resection. We conducted a survival analysis and used logistic regression analysis to assess predictors of non-curative resection. Results A total of 102 ESD were performed on 96 patients. The technical success rate was 100% and the percentage of en-bloc resection was 98%. The percentage of R0 and curative resection was 77.5% (n = 79; 95% CI: 68%-84%) and 63.7% (n = 65; 95% CI: 54%-72%), respectively. The most frequent histology was Barrett-related neoplasia (n = 55 [53.9%]). The main reason for non-curative resection was deep submucosal invasion (n = 25). The centers with a lower volume of ESD obtained worse results in terms of curative resection. The rate of perforation, delayed bleeding and post-procedural stenosis were 5%, 5% and 15.7%, respectively. No patient died or required surgery due to an adverse effect. After a median follow-up of 14 months, 20 patients (20.8%) underwent surgery and/or chemoradiotherapy, and 9 patients died (mortality 9.4%). Conclusions In Spain, esophageal ESD is curative in approximately two out of three patients, with an acceptable risk of adverse events (AU)

A systematic review of (semi-)automatic quality control of T1-weighted MRI scans.

PURPOSE: Artifacts in magnetic resonance imaging (MRI) scans degrade image quality and thus negatively affect the outcome measures of clinical and research scanning. Considering the time-consuming and subjective nature of visual quality control (QC), multiple (semi-)automatic QC algorithms have been developed. This systematic review presents an overview of the available (semi-)automatic QC algorithms and software packages designed for raw, structural T1-weighted (T1w) MRI datasets. The objective of this review was to identify the differences among these algorithms in terms of their features of interest, performance, and benchmarks. METHODS: We queried PubMed, EMBASE (Ovid), and Web of Science databases on the fifth of January 2023, and cross-checked reference lists of retrieved papers. Bias assessment was performed using PROBAST (Prediction model Risk Of Bias ASsessment Tool). RESULTS: A total of 18 distinct algorithms were identified, demonstrating significant variations in methods, features, datasets, and benchmarks. The algorithms were categorized into rule-based, classical machine learning-based, and deep learning-based approaches. Numerous unique features were defined, which can be roughly divided into features capturing entropy, contrast, and normative measures. CONCLUSION: Due to dataset-specific optimization, it is challenging to draw broad conclusions about comparative performance. Additionally, large variations exist in the used datasets and benchmarks, further hindering direct algorithm comparison. The findings emphasize the need for standardization and comparative studies for advancing QC in MR imaging. Efforts should focus on identifying a dataset-independent measure as well as algorithm-independent methods for assessing the relative performance of different approaches.

Implementation of esophageal endoscopic submucosal dissection in Spain: Results from the nationwide registry. / Implementación de la disección endoscópica submucosa esofágica en España: resultados del registro nacional.

INTRODUCTION AND AIMS: The outcomes of endoscopic submucosal dissection (ESD) in the esophagus have not been assessed in our country. Our primary aim was to analyze the effectiveness and safety of the technique. MATERIAL AND METHODS: Analysis of the prospectively maintained national registry of ESD. We included all superficial esophageal lesions removed by ESD in 17 hospitals (20 endoscopists) between January 2016 and December 2021. Subepithelial lesions were excluded. The primary outcome was curative resection. We conducted a survival analysis and used logistic regression analysis to assess predictors of non-curative resection. RESULTS: A total of 102 ESD were performed on 96 patients. The technical success rate was 100% and the percentage of en-bloc resection was 98%. The percentage of R0 and curative resection was 77.5% (n=79; 95%CI: 68%-84%) and 63.7% (n=65; 95%CI: 54%-72%), respectively. The most frequent histology was Barrett-related neoplasia (n=55 [53.9%]). The main reason for non-curative resection was deep submucosal invasion (n=25). The centers with a lower volume of ESD obtained worse results in terms of curative resection. The rate of perforation, delayed bleeding and post-procedural stenosis were 5%, 5% and 15.7%, respectively. No patient died or required surgery due to an adverse effect. After a median follow-up of 14months, 20patients (20.8%) underwent surgery and/or chemoradiotherapy, and 9 patients died (mortality 9.4%). CONCLUSIONS: In Spain, esophageal ESD is curative in approximately two out of three patients, with an acceptable risk of adverse events.

Underwater versus conventional EMR of large nonpedunculated colorectal lesions: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Underwater EMR (UEMR) is an alternative procedure to conventional EMR (CEMR) to treat large, nonpedunculated colorectal lesions (LNPCLs). In this multicenter, randomized controlled clinical trial, we aimed to compare the efficacy and safety of UEMR versus CEMR on LNPCLs. METHODS: We conducted a multicenter, randomized controlled clinical trial from February 2018 to February 2020 in 11 hospitals in Spain. A total of 298 patients (311 lesions) were randomized to the UEMR (n = 149) and CEMR (n = 162) groups. The main outcome was the lesion recurrence rate in at least 1 follow-up colonoscopy. Secondary outcomes included technical aspects, en bloc resection rate, R0 resection rates, and adverse events, among others. RESULTS: There were no differences in the overall recurrence rate (9.5% UEMR vs 11.7% CEMR; absolute risk difference, -2.2%; 95% CI, -9.4 to 4.9). However, considering polyp sizes between 20 and 30 mm, the recurrence rate was lower for UEMR (3.4% UEMR vs 13.1% CEMR; absolute risk difference, -9.7%; 95% CI, -19.4 to 0). The R0 resection showed the same tendency, with significant differences favoring UEMR only for polyps between 20 and 30 mm. Overall, UEMR was faster and easier to perform than CEMR. Importantly, the techniques were equally safe. CONCLUSIONS: UEMR is a valid alternative to CEMR for treating LNPCLs and could be considered the first option of treatment for lesions between 20 and 30 mm due to its higher en bloc and R0 resection rates. (Clinical trial registration number: NCT03567746.).

Esophageal fish bone impaction: the importance of early diagnosis and treatment to avoid severe complications

Esophageal fish bone impaction (EFBI) is a common reason for presentation in the Emergency Department and afrequent indication for urgent esophagogastroduodenoscopy (EGD). Although it is usually effectively diagnosed andtreated by EGD, a confirmed diagnosis prior to the endoscopy is rare as blood tests, radiography and direct laryngoscopy are usually normal. We herein report three cases ofEFBI. Two patients had been previously discharged withouta correct diagnosis. In one case, the patient had a severecomplication that required urgent surgery which could haveprobably been averted with an early diagnosis. Remarkably, a cervical computed tomography (CT) scan was key todiagnose the EFBI in one case and a large retroesophagealabscess in another cases, thus guiding their management.Both patients, who underwent an urgent EGD, had a favorable outcome without the need for hospitalization. Therefore, meticulous anamnesis, adequate imaging and urgentEGD are key to treat patients with EFBI. (AU)

Esophageal fish bone impaction: the importance of early diagnosis and treatment to avoid severe complications.

Esophageal fish bone impaction (EFBI) is a common reason for presentation in the emergency department and a frequent indication for urgent esophagogastroduodenoscopy (EGD). Although it is usually effectively diagnosed and treated by EGD, a confirmed diagnosis prior to the endoscopy is rare as blood tests, radiography and direct laryngoscopy are usually normal. We herein report three cases of EFBI. Two patients had been previously discharged without a correct diagnosis. In one case, the patient had a severe complication that required urgent surgery which could have probably been averted with an early diagnosis. Remarkably, a cervical CT scan was key to diagnose the EFBI in one case and a large retroesophageal abscess in another cases, thus guiding their management. Both patients that underwent an urgent EGD had a favorable outcome without the need for hospitalization. Therefore, meticulous anamnesis, adequate imaging and urgent EGD are key to treat patients with EFBI.

Prevalence of missed lesions in patients with inadequate bowel preparation through a very early repeat colonoscopy.

OBJECTIVES: When bowel preparation (BP) is inadequate, international guidelines recommend repeating the colonoscopy within 1 year to avoid missing clinically relevant lesions. We aimed to determine the rate of missed lesions in patients with inadequate BP through a very early repeat colonoscopy with adequate BP. METHODS: Post hoc analysis was conducted using data collected from a prospective multicenter randomized clinical trial including patients with inadequate BP and then repeat colonoscopy. Inadequate BP was defined as the Boston Bowel Preparation Scale (BBPS) score <2 points in any segment. We included patients with any indication for colonoscopy. The adenoma detection rate (ADR), advanced ADR (AADR), and serrated polyp detection rate (SPDR) were calculated for index and repeat colonoscopies. RESULTS: Of the 651 patients with inadequate BP from the original trial, 413 (63.4%) achieved adequate BP on repeat colonoscopy. The median interval between index and repeat colonoscopies was 28 days. On repeat colonoscopy, the ADR was 45.3% (95% confidence interval [CI] 40.5-50.1%), the AADR was 10.9% (95% CI 8.1-14.3%), and the SPDR was 14.3% (95% CI 10.9-17.7%). Cancer was discovered in four patients (1%; 95% CI 0.2-2.5%). A total of 60.2% of all advanced adenoma (AA) were discovered on repeat colonoscopy. A colon segment scored BBPS = 0 had most AA (66.1%) and all four cancers. CONCLUSION: Patients with inadequate BP present a high rate of AAs on repeat colonoscopy. When a colonoscopy has a colon segment score BBPS = 0, we recommend repeating the colonoscopy as soon as possible.

Compound Endoscopic Morphological Features for Identifying Non-Pedunculated Lesions ≥20 mm with Intramucosal Neoplasia.

BACKGROUND: The major limitation of piecemeal endoscopic mucosal resection (EMR) is the inaccurate histological assessment of the resected specimen, especially in cases of submucosal invasion. OBJECTIVE: To classify non-pedunculated lesions ≥20 mm based on endoscopic morphological features, in order to identify those that present intramucosal neoplasia (includes low-grade neoplasia and high-grade neoplasia) and are suitable for piecemeal EMR. DESIGN: A post-hoc analysis from an observational prospective multicentre study conducted by 58 endoscopists at 17 academic and community hospitals was performed. Unbiased conditional inference trees (CTREE) were fitted to analyse the association between intramucosal neoplasia and the lesions' endoscopic characteristics. RESULT: 542 lesions from 517 patients were included in the analysis. Intramucosal neoplasia was present in 484 of 542 (89.3%) lesions. A conditional inference tree including all lesions' characteristics assessed with white light imaging and narrow-band imaging (NBI) found that ulceration, pseudodepressed type and sessile morphology changed the accuracy for predicting intramucosal neoplasia. In ulcerated lesions, the probability of intramucosal neoplasia was 25% (95%CI: 8.3-52.6%; p < 0.001). In non-ulcerated lesions, its probability in lateral spreading lesions (LST) non-granular (NG) pseudodepressed-type lesions rose to 64.0% (95%CI: 42.6-81.3%; p < 0.001). Sessile morphology also raised the probability of intramucosal neoplasia to 86.3% (95%CI: 80.2-90.7%; p < 0.001). In the remaining 319 (58.9%) non-ulcerated lesions that were of the LST-granular (G) homogeneous type, LST-G nodular-mixed type, and LST-NG flat elevated morphology, the probability of intramucosal neoplasia was 96.2% (95%CI: 93.5-97.8%; p < 0.001). CONCLUSION: Non-ulcerated LST-G type and LST-NG flat elevated lesions are the most common non-pedunculated lesions ≥20 mm and are associated with a high probability of intramucosal neoplasia. This means that they are good candidates for piecemeal EMR. In the remaining lesions, further diagnostic techniques like magnification or diagnostic +/- therapeutic endoscopic submucosal dissection should be considered.

A deep learning approach for synthetic MRI based on two routine sequences and training with synthetic data.

BACKGROUND AND OBJECTIVE: Synthetic magnetic resonance imaging (MRI) is a low cost procedure that serves as a bridge between qualitative and quantitative MRI. However, the proposed methods require very specific sequences or private protocols which have scarcely found integration in clinical scanners. We propose a learning-based approach to compute T1, T2, and PD parametric maps from only a pair of T1- and T2-weighted images customarily acquired in the clinical routine. METHODS: Our approach is based on a convolutional neural network (CNN) trained with synthetic data; specifically, a synthetic dataset with 120 volumes was constructed from the anatomical brain model of the BrainWeb tool and served as the training set. The CNN learns an end-to-end mapping function to transform the input T1- and T2-weighted images to their underlying T1, T2, and PD parametric maps. Then, conventional weighted images unseen by the network are analytically synthesized from the parametric maps. The network can be fine tuned with a small database of actual weighted images and maps for better performance. RESULTS: This approach is able to accurately compute parametric maps from synthetic brain data achieving normalized squared error values predominantly below 1%. It also yields realistic parametric maps from actual MR brain acquisitions with T1, T2, and PD values in the range of the literature and with correlation values above 0.95 compared to the T1 and T2 maps obtained from relaxometry sequences. Further, the synthesized weighted images are visually realistic; the mean square error values are always below 9% and the structural similarity index is usually above 0.90. Network fine tuning with actual maps improves performance, while training exclusively with a small database of actual maps shows a performance degradation. CONCLUSIONS: These results show that our approach is able to provide realistic parametric maps and weighted images out of a CNN that (a) is trained with a synthetic dataset and (b) needs only two inputs, which are in turn obtained from a common full-brain acquisition that takes less than 8 min of scan time. Although a fine tuning with actual maps improves performance, synthetic data is crucial to reach acceptable performance levels. Hence, we show the utility of our approach for both quantitative MRI in clinical viable times and for the synthesis of additional weighted images to those actually acquired.

Implementation of endoscopic submucosal dissection in a country with a low incidence of gastric cancer: Results from a prospective national registry.

INTRODUCTION: Endoscopic submucosal dissection (ESD) has become the treatment of choice for early gastric malignancies. In recent years, the ESD technique has been implemented in Western countries with increasing use. OBJECTIVES: To describe the results of gastric ESD in a Western country with a low incidence of gastric cancer. PATIENTS AND METHODS: The prospective national registry was conducted over 4 years in 23 hospitals, including 30 endoscopists. Epithelial and subepithelial lesions (SEL) qualified to complete removal with ESD were assessed. The technique, instruments, and solution for submucosal injection varied at the endoscopist's discretion. ESD was defined as difficult when: en-bloc resection was not achieved, had to be converted to a hybrid resection, lasted more than 2 h or an intraprocedural perforation occurred. Additionally, independent risk factors for difficult ESD were analyzed. RESULTS: Two hundred and thirty gastric ESD in 225 patients were performed from January 2016 to December 2019 (196 epithelial and 34 SEL). Most lesions were located in the lower stomach (111; 48.3%). One hundred and twenty-eight (55.6%) ESD were considered difficult. The median procedure time was 105 min (interquartile range [IQR]: 60-150). The procedure time for SEL was shorter than for epithelial lesions (90 min [45-121] vs. 110 min [62-160]; p = 0.038). En-bloc, R0, and curative resection rates were 91.3%, 75.2%, and 70.9%, respectively. Difficult ESD had lower R0 resection rates than ESD that did not meet the difficulty criteria (64.8% and 87.6%; p = 0.000, respectively). Fibrosis and poor maneuverability were independent factors associated with difficult ESD (OR 3.6, 95%CI 1.1-11.74 and OR 5.07, 95%CI 1.6-16.08; respectively). CONCLUSIONS: Although the number of cases is limited, the results of this analysis show acceptable en-bloc and R0 rates in gastric ESD considering the wide variability in experience among the operators. Fibrosis and poor maneuverability were associated with more difficulty in completing ESD.

Success, safety, and usefulness of right colon retroflexion for the detection of additional colonic lesions not visualized with standard frontal view.

BACKGROUND: Missed adenomas are the main concern for endoscopists. Right colon retroflexion (RCR) seems to increase the adenoma detection rate (ADR), but important variation in success and usefulness of this maneuver has been reported in the literature AIMS: Primary objective: to assess additional adenoma detection rate (AADR) detected during the RCR attempt. Secondary objectives: to assess success rates of RCR, variables associated with it, and safety of RCR. METHODS: This is a prospective, unicentric, non-randomized study. Consecutive colonoscopies done by six endoscopists (3 of them with < 3 years of experience and 3 with > 3 years) from March to May 2017 were included. Olympus colonoscopes were used (CF-H190, CF-H180) Demographic, clinical, and endoscopic variables were collected. RESULTS: 463 colonoscopies were included. RCR success rate was 93.1% (431/463 colonoscopies). Forty additional lesions were visualized during RCR in 34/463 colonoscopies (7.3%). Additional adenomas were detected in 31/463 colonoscopies (6.7%; OR 0.07). HISTOLOGY: low-grade dysplasia adenomas in 29/40 (72.5%) lesions; 3/40 (7.5%), adenomas with high-grade dysplasia; and 7/40 (17.5%) sessile serrated lesions. Additional adenoma detection contributed to modify the colonoscopy surveillance interval in 25 patients (5.4% of the cohort). Variables associated with RCR success in multivariate analysis were no previous abdominal surgery, length of colonoscope insertion in cecum < 80 cm, and use of Olympus 190 series colonoscopes. No differences between endoscopists' experience were found. RCR was a safe maneuver, with no adverse events in our study. CONCLUSIONS: RCR is a feasible and safe maneuver that can increase ADR, so its routine inclusion in colonoscopy practice should be considered.

The Answer to "When to Clip" After Colorectal Endoscopic Mucosal Resection Based on a Cost-Effectiveness Analysis.

INTRODUCTION: Delayed bleeding (DB) is the most common major complication of endoscopic mucosal resection (EMR). Two randomized clinical trials recently demonstrated that clip closure after EMR of large nonpedunculated colorectal polyps (LNPCPs) reduces the risk of DB. We analyzed the cost-effectiveness of this prophylactic measure. METHODS: EMRs of LNCPCPs were consecutively registered in the ongoing prospective multicenter database of the Spanish EMR Group from May 2013 until July 2017. Patients were classified according to the Spanish Endoscopy Society EMR group (GSEED-RE2) DB risk score. Cost-effectiveness analysis was performed for both Spanish and US economic contexts. The average incremental cost-effectiveness ratio (ICER) thresholds were set at 54,000 € or $100,000 per quality-adjusted life year, respectively. RESULTS: We registered 2,263 EMRs in 2,130 patients. Applying their respective DB relative risk reductions after clip closure (51% and 59%), the DB rate decreased from 4.5% to 2.2% in the total cohort and from 13.7% to 5.7% in the high risk of the DB GSEED-RE2 subgroup. The ICERs for the universal clipping strategy in Spain and the United States, 469,706 € and $1,258,641, respectively, were not cost effective. By contrast, selective clipping in the high-risk of DB GSEED-RE2 subgroup was cost saving, with a negative ICER of -2,194 € in the Spanish context and cost effective with an ICER of $87,796 in the United States. DISCUSSION: Clip closure after EMR of large colorectal lesions is cost effective in patients with a high risk of bleeding. The GSEED-RE2 DB risk score may be a useful tool to identify that high-risk population.

Small Bowel Enteroscopy - A Joint Clinical Guideline from the Spanish and Portuguese Small Bowel Study Groups.

The present evidence-based guidelines are focused on the use of device-assisted enteroscopy in the management of small-bowel diseases. A panel of experts selected by the Spanish and Portuguese small bowel study groups reviewed the available evidence focusing on the main indications of this technique, its role in the management algorithm of each indication and on its diagnostic and therapeutic yields. A set of recommendations were issued accordingly.

Estas recomendações baseadas na evidência detalham o uso da enteroscopia assistida por dispositivo no manejo clínico das doenças do intestino delgado. Um conjunto de Gastrenterologistas diferenciados em patologia do intestino delgado foi selecionado pelos grupos de estudos Espanhol e Portugués de intestino delgado para rever a evidência disponível sobre as principais indicações desta técnica, o seu papel nos algoritmos de manejo de cada indicação e sobre o seu rendimento diagnóstico e terapêutico. Foi gerado um conjunto de recomendações pelos autores.

Educational nurse-led telephone intervention shortly before colonoscopy as a salvage strategy after previous bowel preparation failure: a multicenter randomized trial.

BACKGROUND: The most important predictor of unsuccessful bowel preparation is previous failure. For those patients with previous failure, we hypothesized that a nurse-led educational intervention by telephone shortly before the colonoscopy appointment could improve cleansing efficacy. METHODS: We performed a multicenter, endoscopist-blinded, randomized controlled trial. Consecutive outpatients with previous inadequate bowel preparation were enrolled. Both groups received the same standard bowel preparation protocol. The intervention group also received reinforced education by telephone within 48 hours before the colonoscopy. The primary outcome was effective bowel preparation according to the Boston Bowel Preparation Scale. Intention-to-treat (ITT) analysis included all randomized patients. Per-protocol analysis included patients who could be contacted by telephone and the control cases. RESULTS: 657 participants were recruited by 11 Spanish hospitals. In the ITT analysis, there was no significant difference between the intervention and control groups in the rate of successful bowel preparation (77.3 % vs. 72 %; P = 0.12). In the intervention group, 267 patients (82.9 %) were contacted by telephone. Per-protocol analysis revealed significantly improved bowel preparation in the intervention group (83.5 % vs. 72.0 %; P = 0.001). CONCLUSION: Among all patients with previous inadequate bowel preparation, nurse-led telephone education did not result in a significant improvement in bowel cleansing. However, in the 83 % of patients who could be contacted, bowel preparation was substantially improved. Phone education may therefore be a useful tool for improving the quality of bowel preparation in those cases.

Small bowel enteroscopy - A joint clinical guideline by the Spanish and Portuguese small-bowel study groups

The present evidence-based guidelines are focused on the use of device-assisted enteroscopy in the management of small-bowel diseases. A panel of experts selected by the Spanish and Portuguese small-bowel study groups reviewed the available evidence focusing on the main indications of this technique, its role in the management algorithm of each indication, and its diagnostic and therapeutic yield. A set of recommendations was issued accordingly

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Small bowel enteroscopy - A joint clinical guideline by the Spanish and Portuguese small-bowel study groups.

The present evidence-based guidelines are focused on the use of device-assisted enteroscopy in the management of small-bowel diseases. A panel of experts selected by the Spanish and Portuguese small-bowel study groups reviewed the available evidence focusing on the main indications of this technique, its role in the management algorithm of each indication, and its diagnostic and therapeutic yield. A set of recommendations was issued accordingly.

Determination of optimized set of b-values for Apparent Diffusion Coefficient mapping in liver Diffusion-Weighted MRI.

In this manuscript we derive the Cramér-Rao Lower Bound (CRLB) of the monoexponential diffusion-weighted signal model under a realistic noise assumption, and propose a formulation to obtain optimized sets of b-values that maximize the noise performance of the Apparent Diffusion Coefficient (ADC) maps given a target ADC and a signal-to-noise ratio. Therefore, for various sets of parameters (S0 and ADC), signal-to-noise ratios (SNR) and noise distribution, we computed optimized sets of b-values using CRLB-based analysis in two different ways: (i) through a greedy algorithm where b-values from a pool of candidates were added iteratively to the set, and (ii) through a two b-value search algorithm were all two b-value combinations of the pool of candidates were tested. Further, optimized sets of b-values were computed from synthetic data, phantoms, and in-vivo liver diffusion-weighted imaging (DWI) experiments to validate the CRLB-based analysis. The optimized sets of b-values obtained through the proposed CRLB-based analysis showed good agreement with the optimized sets obtained experimentally from synthetic, phantoms, and in-vivo liver data. The variance of the ADC maps decreased when employing the optimized set of b-values compared to various sets of b-values proposed in the literature for in-vivo liver DWI, although differences of notable magnitude between noise models and optimization strategies were not found. In addition, the higher b-values decreased for lower SNR under the Rician noise distribution. Optimization of the set b-values is critical to maximize the noise performance (i.e., maximize the precision and minimize the variance) of the estimated ADC maps in diffusion-weighted MRI. Hence, the proposed approach may help to optimize and standardize liver diffusion-weighted MRI acquisitions by computing optimized set of b-values for a given set of parameters.