Contrast-Enhanced Ultrasound in the Evaluation of Complex Renal Cystic Lesions: A Scoping Review of CEUS-Adapted Bosniak Classification, Qualitative Imaging Features and Quantitative Time–Intensity Curve Analysis

R Korczyk 12.09.2026

Introduction

Complex renal cystic lesions represent an important diagnostic challenge, as they encompass a broad spectrum of entities, ranging from benign lesions requiring no treatment to cystic-solid renal masses with malignant potential. On B-mode ultrasound, differentiating a simple cyst from a lesion with more complex architecture may be difficult, particularly when subtle septa, wall thickening, mural nodules or solid components are present. Identification of such features usually requires further contrast-enhanced imaging, most commonly contrast-enhanced computed tomography (CECT) or magnetic resonance imaging (MRI) (8–11,59–63).

The Bosniak classification remains the fundamental system for risk stratification of cystic renal lesions. It was originally developed for contrast-enhanced CT and was later adapted to MRI. Its key element is the assessment of enhancement within the cyst wall, septa, mural nodules and solid components, because the presence of vascularity is one of the most important factors influencing risk category and subsequent clinical management. The greatest diagnostic and therapeutic uncertainty concerns intermediate categories, particularly Bosniak IIF and III, where the boundary between surveillance and intervention remains clinically challenging (9–11).

Contrast-enhanced ultrasound enables dynamic real-time assessment of microvascularity using intravascular microbubble contrast agents. Compared with conventional Doppler imaging, CEUS is more sensitive in detecting slow flow and subtle microvascularity, which may facilitate evaluation of thin septa, cyst walls and small mural nodules. Additional advantages include the absence of ionizing radiation and the lack of typical nephrotoxicity associated with iodinated CT contrast agents. Therefore, CEUS may be particularly useful in patients with contraindications to iodinated contrast, chronic kidney disease or the need for repeated follow-up examinations (1,24,52–58).

At the same time, differences between CEUS, CECT and MRI mean that direct transfer of CT-based Bosniak criteria to contrast-enhanced ultrasound may be problematic. The high temporal resolution and sensitivity of CEUS may lead to detection of very subtle enhancement that is not visible on CECT or MRI. This may improve diagnostic sensitivity, but it may also create a risk of overclassification and potentially unjustified surgical referral (2,5,18–21,30,35–39).

In recent years, an increasing number of studies have compared CEUS with CECT and MRI or have addressed adaptation of the Bosniak classification to contrast-enhanced ultrasound. However, uniform and widely accepted interpretive and reporting criteria remain lacking. Differences between centers concern CEUS protocols, definitions of enhancement, interpretation of intermediate categories and reference standards. The aim of this scoping review is to map the current evidence on the use of CEUS in the diagnosis of complex renal cystic lesions, with particular emphasis on adaptation of the Bosniak classification, comparison with CECT and MRI, and the clinical consequences of the distinct sensitivity profile of CEUS (1–7,12–23,40–45).

Study design

The planned study will be conducted as a scoping review on the use of contrast-enhanced ultrasound in the assessment of complex renal cystic lesions classified within the Bosniak framework. The review will focus on how CEUS has been adapted to Bosniak classification, which qualitative enhancement features are most frequently evaluated, and whether quantitative perfusion parameters, including time–intensity curve (TIC) analysis, are used in this field.

A scoping review design is appropriate because the literature is heterogeneous with respect to CEUS protocols, classification systems, reference standards, study populations and reported diagnostic parameters. The central aim of the project is to determine whether CEUS should be regarded merely as an alternative imaging modality or whether it provides a distinct dynamic microvascular layer that may modify Bosniak categorization compared with CECT or MRI.

Particular attention will be paid to intermediate categories, especially Bosniak IIF and III, where clinical decisions are most uncertain, and to the risk of overclassification resulting from the high sensitivity of CEUS for subtle enhancement in septa, cyst walls or mural nodules (2,5,35,40–43).

Methodological framework

Type of review

This study will be designed as a scoping review conducted in accordance with PRISMA-ScR recommendations (67,68).

This review type is most appropriate because the aim is not to calculate a single pooled estimate of CEUS sensitivity or specificity, but rather to map the current state of evidence, identify the main types of available studies, define knowledge gaps and organize how the literature describes CEUS-adapted Bosniak classification and quantitative perfusion analysis.

Data sources

The planned data sources are:

Scopus
- main CEUS-Bosniak search;
- supplementary search for TIC / quantitative CEUS / perfusion.
ScienceDirect
- main search addressing CEUS, renal cystic lesions and Bosniak classification.
Google Scholar
- supplementary source for recent publications, online-ahead-of-print articles, reviews, citation tracking and potentially missed records.

Time frame

The proposed time frame is:

2015–2026

This range was selected because it includes the period before and after the introduction of Bosniak v2019, while also capturing the development of newer CEUS-Bosniak concepts, the EFSUMB 2020 proposal, quantitative CEUS analyses and multiparametric ultrasound techniques (1,9,10,44,45,47–50).

Language

The main extraction will include publications in English. Non-English publications may be noted as potentially relevant but will be excluded from the main extraction because of feasibility of full-text assessment and comparability of extracted data.

Types of eligible publications

The review may include:

retrospective studies;
prospective studies;
comparative studies of CEUS versus CECT/MRI;
studies using histopathology or follow-up as a reference standard;
narrative and systematic reviews;
meta-analyses;
expert statements or position statements;
technical studies on quantitative CEUS, TIC, perfusion analysis or fractional vascularity.

Single case reports will generally not be included in the main extraction unless they address a particularly relevant methodological concept, such as TIC analysis in cystic or cystic-solid renal lesions.

Research question according to PIRD

P — Population / Problem

Adult patients with complex renal cystic lesions or cystic-solid renal lesions assessed within the Bosniak classification framework.

This includes:

complex renal cysts;
complex renal cystic lesions;
cystic renal masses;
solid-cystic renal lesions;
Bosniak IIF, III and IV lesions;
lesions indeterminate on B-mode ultrasound, CECT or MRI;
patients requiring surveillance, further diagnostic work-up or urological assessment.

I — Index test / Intervention

Contrast-enhanced ultrasound, including:

CEUS-adapted Bosniak classification;
qualitative assessment of enhancement in the wall, septa, mural nodules and solid components;
assessment of wash-in and wash-out patterns;
quantitative CEUS analysis;
time–intensity curve parameters;
perfusion analysis;
fractional vascularity;
multiparametric ultrasound when CEUS is used as a reference standard or comparative modality.

R — Reference standard

Reference standards may include:

histopathology;
CECT;
MRI / contrast-enhanced MRI;
stability or progression during clinical follow-up;
imaging follow-up;
therapeutic decision or treatment outcome;
comparison with CT/MRI-based Bosniak classification.

Because reference standards in scoping reviews may be heterogeneous, one of the objectives will be to map which reference standards are used across studies.

D — Diagnosis / Diagnostic outcome

The diagnostic outcomes of interest include:

Bosniak category assignment;
differentiation between benign and malignant lesions;
detection of true vascularity in the wall, septa, nodules or solid components;
upgrading or downgrading of Bosniak category compared with CECT/MRI;
identification of features associated with malignancy risk;
assessment of the usefulness of quantitative CEUS/TIC parameters;
impact of CEUS on clinical decisions: surveillance, further imaging, urological consultation, biopsy or surgical treatment.

Main research question

In adult patients with complex renal cystic lesions or cystic renal masses assessed within the Bosniak framework, how is contrast-enhanced ultrasound used to characterize lesion enhancement and risk category, what reference standards are applied, and which qualitative and quantitative CEUS features are reported as diagnostically or clinically useful?

Short research question for the protocol

What is the current evidence on the role of CEUS in the assessment of complex renal cystic lesions within the Bosniak classification framework, including CEUS-adapted qualitative criteria, comparison with CT/MRI or histopathology, and the use of quantitative time–intensity curve or perfusion parameters?

Primary objective

The primary objective of this scoping review is to map the current evidence on the use of contrast-enhanced ultrasound in the assessment of complex renal cystic lesions within the Bosniak classification framework, with particular emphasis on CEUS-adapted qualitative criteria, comparison with CECT/MRI and histopathology, CEUS-related reclassification or overclassification, and the potential role of quantitative perfusion parameters, including time–intensity curve analysis.

Specific objectives

To determine how the Bosniak classification has been defined and applied in CEUS.
To identify the most frequently assessed qualitative CEUS features, including:
- wall enhancement;
- septal enhancement;
- septal thickness and irregularity;
- mural nodules;
- solid components;
- wash-in;
- wash-out;
- homogeneous or heterogeneous enhancement.
To assess how often CEUS changes Bosniak category compared with CECT or MRI, particularly in Bosniak IIF, III and IV lesions.
To map reference standards used in the studies, including histopathology, CECT, MRI, imaging follow-up and clinical follow-up.
To identify which quantitative CEUS/TIC parameters are reported, including:
- time to peak;
- peak intensity;
- area under the curve;
- wash-in slope;
- wash-out slope;
- mean transit time;
- enhancement ratio;
- fractional vascularity.
To assess whether quantitative CEUS/TIC represents a mature diagnostic tool or remains a promising but still experimental adjunct to qualitative assessment.
To identify major evidence gaps, particularly regarding:
- CEUS-Bosniak standardization;
- interobserver agreement;
- risk of overclassification;
- lack of a uniform reference standard;
- limited number of prospective studies;
- insufficient validation of TIC parameters.
To propose a practical interpretive framework integrating B-mode ultrasound, CEUS, CECT/MRI, follow-up and urological decision-making.

Proposed protocol statement

This scoping review will systematically map the available evidence on CEUS in complex renal cystic lesions assessed within the Bosniak framework. The review will focus on how CEUS-specific enhancement features are defined and reported, how CEUS compares with CECT, MRI, histopathology or follow-up, and whether quantitative perfusion parameters such as TIC-derived metrics or fractional vascularity provide additional diagnostic value. Given the heterogeneity of study designs, imaging protocols, Bosniak adaptations and reference standards, a scoping review methodology will be used to identify evidence patterns, knowledge gaps and potential directions for future standardization.

Data sources and search strategy

The literature review will be conducted as a scoping review using several complementary data sources to capture publications on the use of CEUS in complex renal cystic lesions classified within the Bosniak system. The main searches will be conducted in Scopus and ScienceDirect, while Google Scholar will be used as a supplementary source, particularly to identify recent publications, online-ahead-of-print articles, narrative reviews, citation links and articles potentially missed by the main bibliographic databases.

The search time frame will cover 2015–2026. This interval was selected because it covers the recent development of the Bosniak classification, including Bosniak v2019, recommendations and expert statements concerning CEUS adaptation, and the increasing number of studies comparing CEUS with CECT, MRI, histopathology and clinical follow-up (1,9,10,12–23).

The first search stage will focus on three core concepts: contrast-enhanced ultrasound, renal cystic lesions and Bosniak classification. In Scopus, the following search strategy will be used:

TITLE-ABS-KEY (“contrast-enhanced ultrasound” OR CEUS OR “contrast enhanced ultrasonography”)

AND TITLE-ABS-KEY (“renal cyst” OR “renal cystic lesion” OR “cystic renal mass” OR “complex renal cyst” OR “cystic renal lesion”)

AND TITLE-ABS-KEY (Bosniak OR “Bosniak classification” OR “Bosniak category”)

This search will constitute the core strategy for identifying publications on CEUS-Bosniak. In the preliminary Scopus search, 96 records were retrieved. After filters for years 2015–2026, article/review document type, medicine subject area and English language, 70 records were retained for title and abstract screening.

An analogous search will be performed in ScienceDirect. Because of platform-specific limitations on the number of Boolean operators, a simplified query will be used:

(“contrast-enhanced ultrasound” OR CEUS)

AND (“renal cyst” OR “cystic renal mass” OR “complex renal cyst”)

AND (Bosniak OR “Bosniak classification”)

The preliminary ScienceDirect search retrieved 168 records. After filtering for publications from 2015 onward, English language, research articles and review articles, and medicine as the subject area, 36 records were retained for manual title and abstract screening.

A second supplementary search will focus on quantitative CEUS, time–intensity curve, perfusion and microvascular analysis. Its purpose will be to determine whether quantitative CEUS or TIC parameters have been applied to complex renal cystic lesions and whether these parameters may provide an additional diagnostic layer beyond qualitative CEUS-Bosniak assessment (44,45).

A supplementary Google Scholar search limited to publications from 2026 will be used to identify the most recent studies that may not yet be fully captured in Scopus or ScienceDirect. This search will be treated as complementary and will involve manual screening of titles, abstracts and available text fragments.

All identified publications will be initially assessed by title and abstract. Records will be classified as include, maybe / unclear or exclude. Potentially relevant publications will additionally be assigned to one or more thematic categories: CEUS-Bosniak, CEUS vs CECT/MRI, Bosniak IIF follow-up, Bosniak III/IV and histopathology, quantitative CEUS/TIC/perfusion, multiparametric ultrasound or background only.

Eligibility criteria

Inclusion criteria

Publications will be eligible if they meet the following criteria:

Population and lesion type
- adult patients with complex renal cystic lesions, cystic renal masses or cystic-solid renal lesions;
- lesions assessed in relation to the Bosniak classification, particularly Bosniak IIF, III and IV;
- lesions indeterminate on B-mode ultrasound, CECT or MRI requiring further characterization.
Imaging modality
- studies assessing CEUS in the diagnosis or monitoring of renal cystic lesions;
- studies describing adaptation of the Bosniak classification to CEUS;
- studies comparing CEUS with CECT, MRI, histopathology, imaging follow-up or clinical follow-up;
- studies analyzing qualitative CEUS features such as wall, septal, mural nodule or solid component enhancement, wash-in, wash-out and enhancement heterogeneity;
- studies analyzing quantitative CEUS parameters, including TIC parameters, perfusion analysis, enhancement ratio or fractional vascularity.
Publication type
- retrospective original studies;
- prospective original studies;
- comparative studies;
- studies with histopathological validation;
- studies using follow-up as reference standard;
- narrative reviews, systematic reviews and meta-analyses;
- expert documents, society statements or position statements if they address CEUS-Bosniak or renal cystic lesion imaging.
Time frame and language
- publications from 2015–2026;
- English-language publications;
- publications available at least at abstract level, preferably with full text for final extraction.
Thematic relevance
- publications providing data on at least one of the following:
  - CEUS-Bosniak classification;
  - CEUS compared with CECT or MRI;
  - interobserver agreement;
  - diagnostic performance of CEUS;
  - upgrading or downgrading of Bosniak category;
  - Bosniak IIF follow-up;
  - CEUS-histopathology correlation;
  - quantitative CEUS/TIC/perfusion;
  - impact of CEUS on clinical decision-making.

Exclusion criteria

Publications will be excluded from the main extraction if they meet one or more of the following criteria:

Inappropriate lesion type
- studies focusing exclusively on solid renal tumors without a cystic component;
- publications concerning only RCC, angiomyolipoma, oncocytoma or other solid tumors without reference to cystic renal masses or Bosniak classification;
- studies on general renal parenchymal perfusion without focal renal lesion assessment.
Inappropriate method
- studies unrelated to CEUS;
- studies addressing only conventional ultrasound, Doppler, SMI, MFI or other techniques without CEUS as either the investigated or reference modality;
- CT-, MRI- or radiomics-only studies without a CEUS component, unless used as methodological background.
Inappropriate population
- paediatric studies, unless they provide relevant methodological information applicable to adults;
- studies limited to renal transplantation;
- studies addressing inflammatory disease, trauma, ischemia or postoperative complications without relation to renal cystic lesions.
Inappropriate publication type
- letters without clinical data;
- comments or short opinions without methodological relevance;
- conference abstracts without sufficient data, unless addressing a highly relevant and current topic;
- single case reports, except those presenting an important methodological concept;
- publications without an available abstract.
Language and time limits
- publications outside 2015–2026, except selected historical background papers;
- non-English publications if reliable full-text assessment is not feasible;
- duplicate records.

Study selection

Study selection will be performed in stages.

In the first stage, all records identified in Scopus, ScienceDirect and Google Scholar will be screened by title and abstract. Publications will be classified as:

include — directly meeting inclusion criteria;
maybe / unclear — potentially relevant but requiring full-text assessment;
exclude — not meeting thematic, methodological, language or time criteria.

In the second stage, publications marked as include or maybe / unclear will undergo full-text assessment when available. This step will verify whether the study actually concerns complex renal cystic lesions, CEUS, Bosniak classification, comparison with CECT/MRI, histopathology, follow-up or quantitative CEUS analysis.

In the third stage, included publications will be assigned to one or more thematic groups:

CEUS-Bosniak / adaptation of Bosniak classification to CEUS;
CEUS vs CECT/MRI;
Bosniak IIF follow-up;
Bosniak III/IV and histopathology;
quantitative CEUS / TIC / perfusion analysis;
multiparametric ultrasound as CEUS context;
background only / clinical or technical context.

Handling unclear records

Records classified as maybe / unclear will be handled conservatively to avoid premature exclusion of potentially relevant studies. If it is not possible to determine eligibility based on title and abstract alone, the record will be retained for full-text assessment.

Unclear records may include studies that:

address renal masses but do not specify whether cystic lesions were included;
describe CEUS in renal masses without clear information on cystic renal masses;
report quantitative CEUS or TIC but do not specify whether cystic or only solid lesions were analyzed;
refer to Bosniak classification without specifying imaging modality;
are broad reviews in which CEUS-Bosniak may be only one subsection.

After full-text assessment, such records will be finally classified as:

include, if they contain relevant data on CEUS in complex renal cystic lesions;
background only, if they do not meet main extraction criteria but provide relevant clinical, technical or methodological context;
exclude, if they concern only solid tumors, paediatric populations, transplantation, general renal perfusion or techniques unrelated to CEUS-Bosniak.

Data extraction

Data extraction will be performed from publications included after title, abstract and, when necessary, full-text screening. The main extraction will focus on studies addressing CEUS in complex renal cystic lesions classified within the Bosniak framework and studies comparing CEUS with CECT, MRI, histopathology or follow-up.

Data will be extracted from full texts whenever possible. If full text is unavailable, abstract-only extraction will be performed only when sufficient information is available to classify the study and describe its role in the evidence map. Review articles, expert statements and recommendations will be used mainly to describe context, definitions, CEUS adaptation of Bosniak classification and evidence gaps. Original studies will form the basis for extraction of population, imaging protocol, CEUS features, reference standard and diagnostic performance data.

A structured extraction table will be used. For each publication, the following domains will be recorded:

bibliographic data;
study design;
population and lesion characteristics;
CEUS protocol and interpretation;
qualitative CEUS features;
quantitative CEUS / TIC / perfusion parameters;
Bosniak classification and reclassification;
reference standard;
diagnostic outcomes;
clinical consequences;
study limitations.

Unclear or missing information will be marked as “not reported”, “unclear” or “to be verified in full text” to avoid overinterpretation.

Extracted data items

1. Bibliographic data

For each publication, the following will be extracted:

authors;
year;
title;
journal;
publication type;
DOI or link, if available;
source database;
search category, e.g. Scopus S1, ScienceDirect S1, Google Scholar 2026 or Scopus S2.

2. Study characteristics

The following study-level data will be collected:

study type: retrospective, prospective, review, meta-analysis, position statement;
single-center or multicenter design;
country or region, if reported;
recruitment period;
number of patients;
number of lesions;
patient selection method;
main study objective.

3. Population and lesion characteristics

The following data will be extracted:

age, if reported;
sex, if reported;
chronic kidney disease or contraindications to CECT/MRI, if reported;
lesion type: complex renal cyst, cystic renal mass, complex cystic renal lesion, solid-cystic lesion;
lesion size;
lesion location;
Bosniak category before CEUS, if available;
Bosniak category after CEUS;
presence of Bosniak IIF, III or IV lesions;
whether the lesion was incidental, surveilled or referred for treatment.

4. CEUS-related data

Extracted CEUS-related information will include:

indication for CEUS;
contrast agent used, if reported;
CEUS protocol, if described;
observation time after contrast injection;
number of readers;
reader experience, if reported;
use of CEUS-Bosniak classification;
use of EFSUMB CEUS-adapted Bosniak classification;
comparison with CECT, MRI, histopathology or follow-up;
assessment of interobserver agreement.

5. Qualitative CEUS features

The main qualitative enhancement features will include:

presence or absence of enhancement;
cyst wall enhancement;
septal enhancement;
number of septa;
septal thickness;
septal irregularity;
wall thickening;
wall irregularity;
mural nodules;
nodule morphology and angle with the wall;
solid components;
enhancement of solid components;
homogeneous or heterogeneous enhancement;
rapid or slow wash-in;
presence or absence of wash-out;
delayed wash-out;
hyper-, iso- or hypoenhancement relative to renal parenchyma.

6. Quantitative CEUS / TIC / perfusion parameters

For studies reporting quantitative analysis, the following parameters will be extracted:

time to peak;
peak intensity;
area under the curve;
wash-in slope;
wash-out slope;
arrival time;
rise time;
mean transit time;
enhancement ratio;
tumor-to-cortex enhancement ratio;
wash-in area under the curve;
wash-out area under the curve;
perfusion index;
fractional vascularity;
sum of enhancing wall and septal thickness;
other author-defined CEUS parameters.

For each parameter, it will be noted whether it was used as an independent diagnostic marker, part of a predictive model, a histopathological comparator or a descriptive feature.

7. Bosniak classification and reclassification

Particular attention will be paid to the impact of CEUS on Bosniak categorization. Extracted data will include:

Bosniak version used;
whether the classification was adapted to CEUS;
categories before CEUS;
categories after CEUS;
frequency of upgrading;
frequency of downgrading;
agreement between CEUS and CECT;
agreement between CEUS and MRI;
agreement between CEUS and histopathology;
categories with the highest discrepancy;
data on potential overclassification.

8. Reference standard

The reference standard will be recorded as:

histopathology;
CECT;
MRI / CEMRI;
imaging follow-up;
clinical follow-up;
lesion stability;
lesion progression;
therapeutic decision;
surgical or ablative treatment;
composite reference standard.

If different reference standards are used for different patient groups, this will be recorded separately.

9. Diagnostic outcomes

When available, the following diagnostic outcomes will be extracted:

sensitivity;
specificity;
positive predictive value;
negative predictive value;
diagnostic accuracy;
AUC;
kappa coefficient;
Gwet’s agreement coefficient;
intraobserver agreement;
interobserver agreement;
malignancy rate in individual Bosniak categories;
benign lesion rate in Bosniak III and IV.

10. Clinical outcomes and decision impact

If reported, data will be extracted on:

change in management after CEUS;
surveillance recommendation;
referral for further CECT/MRI;
urological consultation;
biopsy recommendation;
surgical treatment;
active surveillance of Bosniak IIF lesions;
progression during follow-up;
stability during follow-up;
potential reduction of unnecessary procedures.

11. Study limitations

The following limitations will be recorded:

retrospective design;
small patient number;
small lesion number;
single-center design;
lack of complete histopathological validation;
heterogeneous reference standard;
non-standardized CEUS protocol;
lack of operator experience data;
lack of blinded image review;
absence of interobserver agreement analysis;
short follow-up;
limited number of Bosniak IIF or III lesions;
limited validation of quantitative TIC parameters.

Use of extracted data in synthesis

Extracted data will be used for descriptive synthesis. Because of expected heterogeneity in study design, CEUS protocols, Bosniak classification systems and reference standards, the main aim will not be meta-analysis but mapping of available evidence.

Data will be presented across the following domains:

characteristics of included studies;
adaptation of Bosniak classification to CEUS;
qualitative CEUS features used for risk stratification;
comparison of CEUS with CECT and MRI;
role of CEUS in reclassification of Bosniak IIF–III–IV lesions;
role of CEUS in Bosniak IIF follow-up;
quantitative CEUS/TIC as an emerging adjunctive tool;
evidence gaps and future research needs.

Results will be presented narratively and in tables, with distinction between core studies, contextual publications and studies addressing quantitative CEUS parameters.

Data synthesis

Because of the anticipated heterogeneity of the available literature, data synthesis will be descriptive and consistent with the scoping review design. The aim will not be to perform formal meta-analysis or to calculate a pooled estimate of CEUS diagnostic performance, but to map the scope of evidence, identify major research themes, compare approaches to CEUS-adapted Bosniak classification and highlight evidence gaps.

Data from included publications will be organized into several thematic domains: CEUS-Bosniak, CEUS versus CECT/MRI, Bosniak IIF surveillance, Bosniak III/IV and histopathology, quantitative CEUS/TIC/perfusion, and multiparametric ultrasound context. Within each group, the study type, patient population, lesion characteristics, reference standard, imaging features and main clinical conclusions will be described.

For studies reporting diagnostic performance parameters, including sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy or AUC, these values will be summarized in tables and discussed narratively. Because of differences in study design, inclusion criteria, Bosniak definitions, CEUS protocols and reference standards, these outcomes will not be pooled quantitatively unless full-text analysis demonstrates sufficient methodological homogeneity.

Special attention will be paid to how CEUS affects Bosniak categorization compared with CECT and MRI. Cases of upgrading, downgrading and potential overclassification will be discussed separately, particularly in Bosniak IIF and III lesions. Quantitative CEUS data, including TIC parameters, fractional vascularity and quantitative assessment of enhancing walls or septa, will be presented as a separate emerging evidence domain.

The final synthesis will be narrative and tabular. Its purpose will be to provide a practical map of the current literature and determine whether CEUS should be regarded as a standalone alternative to CECT/MRI, a complementary modality, a problem-solving tool or part of a broader multimodal diagnostic strategy.

Quality of evidence and methodological limitations

In accordance with the scoping review design, formal risk-of-bias assessment of individual studies will not be the primary aim of this work. The review will focus on mapping the available evidence, study scope, definitions, imaging protocols and reference standards rather than hierarchically grading the diagnostic performance of a test.

Nevertheless, key methodological features influencing the reliability of results will be recorded during extraction and interpretation. These will include prospective or retrospective design, single-center or multicenter setting, number of patients and lesions, use of histopathology as reference standard, follow-up duration, image interpretation process, number of readers, operator experience, blinded assessment and reporting of interobserver agreement.

A major limitation of the current literature is heterogeneity of CEUS protocols and differences in the adaptation of Bosniak classification to contrast-enhanced ultrasound. Studies vary in ultrasound equipment, contrast agents, observation time after contrast injection, definitions of enhancement, Bosniak version and criteria for classifying a lesion as benign or malignant. In some studies the reference standard is histopathology, whereas in others it is lesion stability during imaging or clinical follow-up. This may limit comparability of results.

An additional limitation is that CEUS is highly sensitive for detecting subtle vascularity. This feature is both an advantage and a potential source of overclassification, especially in lesions with thin septa, minimal wall enhancement or small mural nodules. Therefore, data on CEUS-related upgrading compared with CECT/MRI should be interpreted cautiously (2,5,35).

There is also a limited number of studies addressing quantitative CEUS/TIC in cystic renal lesions. Preliminary screening indicates that quantitative CEUS is more developed in studies of solid renal tumors than in classical Bosniak cystic lesions. Therefore, TIC, perfusion analysis and fractional vascularity should be interpreted as promising but still preliminary research areas (44,45).

Results

Record identification and study selection

The preliminary literature search was conducted in Scopus, ScienceDirect and, supplementarily, Google Scholar. The search strategy was designed to identify both publications directly addressing CEUS-Bosniak and studies concerning quantitative CEUS, TIC, perfusion and multiparametric ultrasound.

In Scopus, the main CEUS-Bosniak search, designated as Scopus S1, retrieved 96 records. After applying filters for publication years 2015–2026, document type Article/Review, subject area Medicine and language English, 70 records were retained for title and abstract screening.

In ScienceDirect, an analogous search addressing CEUS, renal cystic lesions and Bosniak classification was performed. Because of technical limitations of the platform, a simplified search string was used. The search retrieved 168 records. After filtering for publications from 2015 onward, English language, Research articles and Review articles, and Medicine as the subject area, 36 records were retained for manual screening.

A supplementary Google Scholar search limited to publications from 2026 was performed to identify recent papers not yet fully captured in Scopus or ScienceDirect. This search retrieved 36 records, which were manually assessed by title, abstract and available text fragments.

A second Scopus search, designated as Scopus S2, focused on TIC / quantitative CEUS / perfusion. After applying filters for Medicine, Article/Review and English language, 51 records were identified. Preliminary assessment showed that most addressed solid renal tumors, RCC/AML differentiation, transplantation, paediatrics, general renal perfusion or multiparametric ultrasound. Only a limited number directly addressed complex renal cystic lesions and Bosniak classification.

During preliminary selection, publications were classified as include, maybe / unclear or exclude. Included records addressed CEUS in cystic renal lesions, Bosniak adaptation, CEUS versus CECT/MRI, Bosniak IIF follow-up, histopathological validation of Bosniak III/IV lesions and quantitative CEUS analysis.

Evidence characteristics

The identified literature includes several major evidence categories.

The first and most important group consists of studies directly addressing CEUS-adapted Bosniak classification. These include publications describing adaptation of the Bosniak classification to CEUS, expert statements, interobserver agreement studies and diagnostic performance studies of CEUS-Bosniak (1–7).

The second group includes studies comparing CEUS with CECT and/or MRI in complex renal cystic lesions. These studies are essential for assessing whether CEUS changes Bosniak category, increases detection of subtle enhancement and can serve as a problem-solving tool after indeterminate CT or MRI findings (12–23,25–29).

The third group includes publications on Bosniak IIF surveillance, where CEUS is used as a follow-up tool or as a method for identifying features associated with progression. This group is clinically important because Bosniak IIF lesions are usually not operated on immediately but require regular monitoring (40–43).

The fourth group concerns Bosniak III and IV lesions, often with histopathological validation. These studies are relevant for estimating malignancy risk, the rate of benign lesions in high-risk categories and potential overtreatment (32–39).

The fifth group includes studies on quantitative CEUS, TIC parameters, perfusion analysis and fractional vascularity. Preliminary analysis suggests that this evidence is less developed than qualitative CEUS-Bosniak assessment. The most directly relevant publications concern quantitative CEUS in Bosniak ≥II lesions and fractional vascularity in complex renal cysts (44,45).

The final group consists of contextual publications on multiparametric ultrasound, SMI/MFI, CEUS safety in chronic kidney disease, indications for CEUS in indeterminate renal masses and broad reviews of renal mass imaging (24,47–58,59–66).

Main findings

Preliminary synthesis indicates that CEUS is consistently described as a highly sensitive modality for detecting vascularity in cyst walls, septa, mural nodules and solid components of renal cystic lesions. Because microbubble contrast agents remain intravascular and CEUS provides high temporal resolution, the method enables real-time assessment of microvascularity (1,24,52–58).

The most frequently reported qualitative CEUS features include presence or absence of enhancement, cyst wall enhancement, septal enhancement, septal thickness and irregularity, mural nodules, solid components, homogeneous or heterogeneous enhancement, and wash-in and wash-out patterns. Mural nodules appear particularly important because their presence and morphology may determine assignment to a higher-risk category (3,4).

In several studies, CEUS led to a change in Bosniak category compared with conventional ultrasound, CECT or MRI. This usually resulted from improved visualization of subtle enhancement in thin septa, thickened walls or small mural nodules. This effect may improve detection of potentially malignant lesions, but it may also increase the risk of overclassification, particularly in intermediate categories (2,5,18–21,30,35).

Bosniak IIF remains an important area for CEUS follow-up because CEUS allows surveillance without ionizing radiation and without nephrotoxic contrast agents. Bosniak III remains the most clinically problematic category because it includes both malignant and benign lesions. In this group, CEUS may provide additional information on true vascularity, but interpretation should be cautious and correlated with CECT/MRI and clinical context (32–43).

In quantitative CEUS, the most commonly identified parameters include time to peak, peak intensity, area under the curve, wash-in and wash-out parameters, enhancement ratio and fractional vascularity. However, the number of studies directly addressing cystic renal lesions is limited. At present, quantitative CEUS/TIC should be considered a promising adjunct rather than a mature, standardized component of Bosniak classification (44,45).

CEUS compared with CECT and MRI

Comparisons between CEUS, CECT and MRI suggest that CEUS may have higher sensitivity for detecting subtle enhancement, especially in thin septa, cyst walls and small mural nodules. In some studies, CEUS achieved very high sensitivity and negative predictive value, supporting its usefulness for excluding vascularity and distinguishing avascular cystic content from suspicious enhancing structures (12–23).

At the same time, higher CEUS sensitivity may be associated with lower specificity compared with CECT or MRI. In practice, this means that CEUS may more frequently upgrade Bosniak category, particularly when it detects minimal enhancement that is absent or equivocal on cross-sectional imaging. This issue is central to the review: CEUS may improve classification in some cases, but in others it may overinterpret subtle enhancement (2,5,35).

CECT and MRI therefore remain important reference modalities, especially before therapeutic decisions in Bosniak III and IV lesions. CEUS may serve as a complementary modality, particularly in patients with contraindications to iodinated or gadolinium-based contrast agents, in chronic kidney disease, in Bosniak IIF surveillance and in cases with indeterminate CT/MRI findings (24,25–29,52–58).

Clinical context

The clinical relevance of CEUS in renal cystic lesions results from the combination of high sensitivity for microvascular imaging, safety of microbubble contrast agents and dynamic real-time assessment. CEUS may be particularly useful in patients with chronic kidney disease, contraindications to iodinated or gadolinium-based contrast agents, and those requiring repeated follow-up (24,52–58).

In a practical diagnostic algorithm, B-mode ultrasound may serve as the initial step to distinguish simple cysts from lesions requiring further work-up. CEUS adds a second layer by confirming or excluding true vascularity in septa, walls, mural nodules and solid components. CECT and MRI remain complementary modalities, particularly in suspicious, discordant or pre-treatment cases.

The main clinical challenge is balancing the high sensitivity of CEUS against the risk of overclassification. Detection of very subtle enhancement may improve detection of malignant lesions, but it may also lead to excessive assignment of intermediate lesions to higher-risk categories. Therefore, CEUS should not be interpreted as a simple transfer of CT/MRI Bosniak criteria into ultrasound, but rather as a complementary modality requiring its own interpretive criteria and correlation with cross-sectional imaging and clinical context (1,2,5,35).

Preliminary findings support the concept that CEUS-Bosniak may represent a practical bridge between classical radiological classification and dynamic microvascular assessment in renal cystic lesions. However, the literature also indicates the need for further standardization of CEUS protocols, clear definitions of enhancement, interobserver agreement studies and prospective validation of quantitative parameters (3,4,44,45).

Discussion

The Bosniak classification was developed for the diagnostic evaluation and risk stratification of renal cystic lesions, particularly complex lesions containing septa, wall thickening, calcifications, mural nodules or solid components. Initially, this system was based on assessment of contrast enhancement on computed tomography and was subsequently adapted to magnetic resonance imaging. It currently plays a central role in classifying renal cystic lesions, estimating the likelihood of malignancy and guiding decisions regarding surveillance, additional imaging, urological referral or surgical treatment (8–11).

CEUS is a dynamic imaging technique with high diagnostic potential, mainly because of its temporal resolution and ability to assess enhancement in real time. The diagnostic value of CEUS is closely related to the properties of ultrasound contrast agents. Sulfur hexafluoride microbubbles oscillate under the influence of the ultrasound beam generated by the transducer and remain confined to the vascular compartment. Their small diameter, usually approximately 3–8 μm, allows passage through the microcirculation, making CEUS particularly suitable for evaluating microvascularity in thin septa, cyst walls, mural nodules and solid components (1,24,52–58).

However, an important question remains whether the Bosniak classification can be directly transferred to CEUS without modification and whether CEUS-based categorization is clinically equivalent to CECT- or MRI-based assessment. This issue is particularly relevant for Bosniak III lesions, where the literature indicates a risk of overclassification, especially when lesions previously considered Bosniak II or IIF are upgraded to category III. Such upgrading may result in classification of a lesion as more suspicious and may potentially lead to unnecessary surgical treatment, including nephrectomy in selected cases. For this reason, the concept of CEUS-adapted Bosniak classification remains an area requiring further validation and standardization (2,5,18–21,30,35–39).

The CT-based Bosniak classification relies on assessment of the cyst wall, septa, calcifications, mural nodules, solid components and the presence and character of contrast enhancement. CEUS can evaluate the same structures, but the examination should always be preceded by careful B-mode ultrasound assessment. B-mode imaging provides the first-line evaluation of lesion architecture, including the presence of septa, wall thickening, calcifications, solid components and the technical accessibility of the lesion for reliable contrast-enhanced assessment (30,46).

The nature of contrast enhancement in CEUS differs fundamentally from that in CECT and MRI. CEUS assesses dynamic enhancement with high temporal resolution and in real time. Therefore, it may detect very subtle vascularity in structures that remain equivocal or invisible on CECT or MRI. This supports the rationale for adapting the Bosniak classification to CEUS, but at the same time indicates that CT/MRI-based criteria cannot be translated into CEUS in a simple one-to-one manner. CEUS provides not only morphological information but also a dynamic microvascular layer that requires its own interpretive logic and careful correlation with CECT and MRI (1,2,5,12–23).

The EFSUMB 2020 proposal and the work by Cantisani and colleagues represent one of the most important foundations for standardizing CEUS-Bosniak assessment. This framework adapted Bosniak categorization to CEUS and emphasized the ability of CEUS to demonstrate true vascularity within cyst walls, septa and nodular components. At the same time, it highlighted that CEUS and cross-sectional imaging require modality-specific interpretive criteria and that further validation is particularly needed for lesions classified as Bosniak II, III and IV. Subsequent studies by Möller, Munch and Jin further developed this discussion, suggesting that CEUS should not be regarded merely as an experimental technique but as a clinically relevant method for evaluating complex renal cystic lesions (1–4).

The most important qualitative CEUS features in cystic renal lesions include enhancement of the cyst wall, enhancement of septa, number and thickness of septa, irregularity of the wall or septa, presence of mural nodules and the presence or absence of solid components. The dynamic nature of CEUS also allows assessment of homogeneous or heterogeneous enhancement, contrast arrival, time to peak, wash-in and wash-out patterns, and comparison of lesion enhancement with adjacent renal parenchyma (1–7,18–23).

Low-risk CEUS features include absence of enhancement, thin and smooth septa, absence of a solid component, absence of mural nodularity and lesion stability on follow-up imaging. Intermediate-risk features include multiple thin septa, subtle septal enhancement, minimal wall thickening and equivocal enhancement, which may correspond to Bosniak IIF or III categories. High-risk features include thick or irregular septa, an enhancing mural nodule, a solid component, marked enhancement heterogeneity, enhancement kinetics resembling solid renal tumors and morphology consistent with Bosniak IV lesions (1–7,32–39).

A key decision point is the identification and interpretation of mural nodularity. Jin et al. emphasized that subtle internal or mural protrusions may be difficult to classify reproducibly, particularly when the distinction between a true mural nodule and focal wall thickening is uncertain. The authors highlighted the need to assess the angle between the protruding structure and the cyst wall, as well as its enhancement pattern. Marked enhancement heterogeneity may shift interpretation toward a higher risk category. In this context, mural nodularity is probably one of the most important structures to actively search for and characterize during CEUS-Bosniak assessment. At the same time, it remains one of the most subjective features and is strongly influenced by reader experience and image quality (3,4).

When CEUS is compared with CECT and MRI, the central question is whether its higher sensitivity also generates a clinically relevant risk of overclassification. Several comparative studies have shown that CEUS has very high sensitivity for detecting enhancement, particularly in thin septa, cyst walls, small mural nodules, slow flow and subtle microvascularity. This has been reported in studies comparing CEUS with CECT and/or MRI, including prospective and retrospective series as well as meta-analyses (12–23).

The potential advantage of SonoVue/Lumason or other microbubble contrast agents results from the physical principles of CEUS. CEUS provides high temporal resolution, real-time dynamic imaging and a purely intravascular contrast phase. Consequently, it is highly sensitive for slow flow and microvascular enhancement. However, conventional limitations of ultrasound remain important. These include poor acoustic windows, bowel gas, deep lesion location, obesity, limited patient cooperation, comorbidities and reduced reliability in some anatomical locations (1,24,52–58).

The high sensitivity of CEUS also has a diagnostic cost. Subtle enhancement detected by CEUS may be overinterpreted, and not every minimal enhancing focus necessarily has clinical significance. Audenet et al. drew particular attention to this problem in relation to Bosniak III lesions. CEUS is highly sensitive for microvascularity, but this sensitivity may come at the expense of lower specificity and greater susceptibility to subjective interpretation of wall and septal enhancement. For this reason, CEUS appears to have its greatest potential as a complementary modality rather than as an isolated replacement for CECT or MRI. In high-risk lesions, CEUS findings should be interpreted in correlation with CECT or MRI, and clinical decisions should be based on diagnostic synergy between modalities (2,5,18–21,30,35–39).

Because of the risk of overclassification, particularly in lesions corresponding to Bosniak III, CEUS should not be used as the sole basis for referral to invasive treatment. Instead, it should be integrated into a multimodal diagnostic strategy. A practical approach should begin with careful B-mode assessment of lesion morphology, wall and septal architecture, internal and external contours, calcifications and possible nodularity. This may be followed by Doppler evaluation and CEUS, which enables real-time dynamic assessment of microvascular enhancement. The high sensitivity of CEUS for subtle enhancement is an important diagnostic advantage, but it requires correlation with CECT and/or MRI, especially before urological decision-making in intermediate or suspicious lesions (25–31,32–39).

CECT and MRI should therefore remain important reference modalities for classical Bosniak categorization, whereas CEUS should be regarded as a complementary modality that refines evaluation of vascularity within cyst walls, septa, mural nodules and solid components. In patients in whom CECT or contrast-enhanced MRI is contraindicated, difficult to perform or logistically unavailable, CEUS may have particular value. This applies especially to patients with renal impairment, reduced mobility or severe comorbidity. In such selected but clinically important cases, if the patient may still benefit from invasive treatment, a clearly high-risk CEUS pattern corresponding to Bosniak IV may support urgent urological consultation and treatment planning. In most patients, however, CEUS should be interpreted as part of integrated imaging assessment, together with CECT and/or MRI, clinical status, renal function and patient preferences (24,25–29,52–58).

Clinical decision-making based on CEUS is justified because the method enables detailed assessment of the number and thickness of septa, wall morphology, solid components and true contrast enhancement. These features may support Bosniak categorization and guide management. Nevertheless, the literature repeatedly emphasizes the problem of overdiagnosis, particularly unnecessary upgrading to Bosniak III, which may increase the risk of overtreatment (35–39). The key clinical challenge is therefore to avoid a situation in which the high sensitivity of CEUS is automatically translated into more aggressive treatment.

In this context, biopsy of cystic renal lesions has a limited role. This is mainly because of sampling error, difficulty in targeting the solid or enhancing component and limited impact on management when multimodal imaging findings are concordant. Therefore, decisions regarding invasive treatment should rely primarily on a synthetic multimodal assessment that includes CEUS, CECT and/or MRI, lesion morphology and the clinical context of the patient (36–39,59–66).

Bosniak IIF follow-up

Bosniak IIF remains a separate and clinically important category. CEUS is particularly suitable for reassessment and follow-up of lesions previously identified on B-mode ultrasound, CECT or MRI because microbubble contrast agents have a favorable safety profile. The absence of ionizing radiation, nephrotoxicity and gadolinium exposure makes CEUS suitable for repeated surveillance examinations. Bosniak IIF lesions are not unequivocally benign and require monitoring to exclude progression to a higher Bosniak category, but they usually do not require immediate invasive treatment (40–43).

In Bosniak IIF lesions, CEUS allows detailed assessment of septal and wall vascularity and may be practical for surveillance of stable lesions, especially in patients with multiple renal cysts or limitations to repeated contrast-enhanced CT or MRI. However, follow-up with CEUS also raises interpretive challenges. It remains unclear whether newly detected subtle septal enhancement always represents true progression, which feature should trigger escalation of imaging, and when CECT or MRI should be added. In other words, even if CEUS detects enhancement in a septum that was not previously visible, the clinical significance of this finding may remain uncertain. Current evidence is not yet standardized enough to support fully uniform clinical decision-making in this setting (40–43).

Quantitative CEUS and time–intensity curve analysis

The supplementary search focused on quantitative CEUS, time–intensity curve analysis and perfusion-related parameters indicates that quantitative CEUS is present in the renal imaging literature, but most available studies concern solid renal tumors, differentiation between renal cell carcinoma and angiomyolipoma, RCC grading, transplantation, renal parenchymal perfusion or broadly defined renal masses rather than strictly Bosniak-classified cystic lesions.

In complex renal cystic lesions, the studies by He and Chandrasekar suggest that a quantitative CEUS approach is conceptually attractive, although the evidence remains limited. The work by He et al. is particularly interesting because it evaluated not only classical dynamic enhancement parameters but also quantitative morphological features visible after contrast administration, such as the combined thickness of enhancing walls and septa. This suggests that future quantitative CEUS in cystic renal lesions may rely not only on time–intensity curve parameters but also on objective measurement of enhancing morphological structures (44,45).

In practical terms, this approach requires assessment of which parts of the lesion enhance: the wall, septa, mural nodules or solid components. It also requires quantitative measurement of their thickness, extent or proportional contribution to the lesion. Fractional vascularity and volumetric CEUS may represent additional approaches for estimating the vascularized portion of complex cystic lesions, although their current role remains investigational (44,45).

At present, TIC analysis should be considered a research tool and an adjunct to qualitative assessment rather than a standardized component of CEUS-Bosniak classification. Its clinical application is limited by small study populations, variability in ultrasound equipment and software, non-standardized region-of-interest placement, different reference tissues and the absence of validated cut-off values. Moreover, most quantitative CEUS data concern solid tumors rather than cystic renal lesions. TIC parameters may support interpretation of enhancement dynamics, but they are not yet sufficient for routine decision-making within the Bosniak framework (44,45,47–51,65).

Microvascular imaging and multiparametric ultrasound

Non-contrast microvascular techniques, such as superb microvascular imaging, microvascular flow imaging and related methods, also deserve attention. Studies evaluating these techniques suggest that they may depict subtle vascular signals without the need for contrast administration. This makes them potentially useful as an adjunct to B-mode imaging, as a screening tool or as an alternative in rare patients with contraindications to CEUS contrast agents (47–50).

Their practical advantages may include lower cost when the ultrasound system already includes the required software. However, in available studies, CEUS often remains the reference modality against which microvascular techniques are compared. Therefore, while SMI, MFI and related methods fit well into the future of multiparametric ultrasound, current evidence still supports CEUS as the more direct method for assessing true enhancement and vascularity in complex renal cystic lesions (47–50).

CEUS in patients with chronic kidney disease

Patients with chronic kidney disease, dialysis-dependent patients and patients with acquired cystic kidney disease represent a particularly relevant clinical population. In these patients, CEUS has an important practical advantage because it enables assessment of lesion vascularity without ionizing radiation and without iodinated or gadolinium-based contrast agents, which may be limited or contraindicated in CECT and MRI (24,54–58).

The value of CEUS becomes especially important when repeated imaging is required or when multiple cystic lesions are present. In this population, CEUS may serve not only as a single imaging test but also as part of a broader diagnostic strategy for renal impairment. This is clinically relevant because renal parenchyma may be chronically altered, cysts may be numerous, and the risk of RCC may be increased. CEUS may help distinguish avascular hemorrhagic, proteinaceous or debris-containing cystic content from a truly vascularized tumor component, thereby reducing unnecessary cross-sectional imaging and improving selection of lesions requiring further diagnostic work-up (24,54–58).

Proposed practical algorithm for CEUS use

A practical model for the use of CEUS in renal cystic lesions should begin with careful B-mode assessment, because the quality of baseline ultrasound determines the reliability of further categorization. The first step should include technically adequate imaging of the kidney, documentation of lesion location and size, and optimization of focus, depth, gain and magnification. B-mode ultrasound should assess lesion architecture, including septa, wall thickening, calcifications, solid components and possible nodularity. At this stage, B-mode imaging functions as a selection tool for identifying lesions requiring contrast-enhanced assessment (30,46).

The second step is CEUS targeted at evaluation of true contrast enhancement. The key issue is to determine which lesion components enhance: the wall, septa, focal thickening, mural nodule or solid component. Particular attention should be paid to enhancing nodularity, because this is one of the most important high-risk features and may support categorization as Bosniak IV. At this stage, it may also be useful to assess the thickness of enhancing walls and septa and, when appropriate software is available, to perform supplementary dynamic or quantitative analysis (1–7,44,45).

The third step should be correlation with CECT and/or MRI, especially in high-risk lesions, in discordant cases and when CEUS suggests upgrading compared with previous cross-sectional imaging. CEUS should not be treated as an automatic replacement for classical CT/MRI-based Bosniak classification, but rather as a complementary modality that may refine assessment of true vascularity in walls, septa and nodules. When CEUS and CECT/MRI findings are concordant, diagnostic confidence increases. When results are discordant, lesion morphology, technical quality of imaging and clinical context should be reassessed (8,11–16,25–29).

The fourth step is risk-adapted clinical decision-making. Lesions corresponding to Bosniak IIF should generally remain under surveillance, particularly when stable and without unequivocal progression of enhancement features. In Bosniak III lesions, management should be individualized according to CEUS findings, CECT/MRI correlation, patient age, comorbidity, renal function and patient preference. Lesions corresponding to Bosniak IV require urgent urological consultation, further characterization or consideration of invasive treatment, although final decisions should still arise from multimodal assessment rather than from the isolated result of a single imaging modality (32–43).

Limitations of the current evidence and need for standardization

This scoping review indicates that one of the main limitations of current CEUS-Bosniak assessment is the lack of full standardization of interpretive criteria. Key features such as minimal enhancement, septal thickening, mural nodularity, solid component and wash-out are defined differently across studies. Heterogeneity also concerns CEUS protocols, contrast agent type and dose, machine settings, mechanical index, clip archiving and operator experience. These differences limit direct comparison between studies and make it difficult to establish uniform diagnostic thresholds for CEUS-Bosniak (1–7,12–23).

Another important limitation is the heterogeneity of reference standards. Some studies use histopathology, whereas others rely on imaging follow-up, CECT, MRI or composite reference standards. As a result, study populations are not fully comparable. Verification bias may also be relevant: more suspicious lesions are more likely to undergo surgery and obtain histopathological confirmation, whereas lesions considered benign are usually followed conservatively. This may overestimate malignancy rates in high-risk categories and complicate evaluation of the true predictive value of CEUS (32–39).

The current evidence base is also limited by the relatively small number of prospective studies. Much of the available literature consists of retrospective series, single-center experiences, small cohorts and populations selected for surgical treatment. Validation of quantitative CEUS and TIC parameters remains particularly insufficient. Further development of this field requires standardization of region-of-interest placement, reproducibility assessment, cut-off definition, multicenter validation and comparison with histopathology and long-term follow-up (3,4,21,22,32–35,44,45).

Future research directions

Future research should focus on prospective multicenter studies based on standardized CEUS protocols. Such protocols should specify contrast agent type and dose, scanning technique, ultrasound settings, mechanical index, clip archiving, operator experience and a uniform CEUS-Bosniak categorization system. Parallel comparison with CECT and/or MRI and with a reliable reference standard, including histopathology or sufficiently long imaging follow-up, would be essential (1–7,12–23,32–45).

Mural nodules require particular standardization because they represent one of the major sources of interpretive variability. Future studies should define nodularity more precisely, including how nodules should be measured, how their relationship to the wall or septum should be assessed, what role the angle of attachment should play, and which threshold of enhancement should qualify a lesion as Bosniak IV. Quantitative CEUS also requires further validation, including TIC parameters, enhancement intensity metrics, measurements of enhancing wall and septal thickness, fractional vascularity and models combining qualitative and quantitative enhancement analysis (3,4,44,45).

Another important research direction is to define the role of CEUS within the real clinical pathway of patients with complex renal cystic lesions. Studies should address practical questions: when CEUS alone is sufficient for follow-up, when CECT or MRI should be added, when MRI should serve as the problem-solving modality in discordant cases, when urological referral is required, and when surveillance is safe. The most important question is whether incorporation of CEUS into routine practice improves patient outcomes and diagnostic efficiency. Future studies should assess whether CEUS-based strategies reduce unnecessary surgery, limit CECT use, reduce radiation exposure, enable safer follow-up and improve selection of patients referred for urological treatment — or whether they increase the risk of overclassification (25–29,35–43).

Current evidence suggests that CEUS may both increase upgrading of intermediate lesions and more clearly define lesions that are unequivocally benign or high risk. This may reduce the need for CECT or MRI in selected patients, accelerate clarification of indeterminate B-mode findings and improve differentiation between avascular hemorrhagic, proteinaceous or debris-containing cystic content and truly vascularized tumor components (1–7,25–31,52–58).

Conclusions

CEUS is a valuable diagnostic tool in the assessment of complex renal cystic lesions. Its main advantages include the absence of ionizing radiation, real-time assessment of microvascular enhancement and lack of nephrotoxicity typical of iodinated contrast agents used in CECT. In selected patient groups, especially those with chronic kidney disease or contraindications to contrast-enhanced cross-sectional imaging, CEUS may substantially improve diagnostic options (1,24,52–58).

In clinical practice, CEUS appears particularly useful for identifying clearly benign lesions and high-risk lesions, especially those corresponding to Bosniak I and Bosniak IV categories. It may help eliminate pseudotumors, distinguish avascular cystic content from truly enhancing lesion components and support surveillance of Bosniak IIF lesions. Its value may be especially relevant in patients with chronic kidney disease, multiple renal cysts or a need for repeated follow-up examinations (24,40–43,52–58).

At the same time, the high sensitivity of CEUS for subtle enhancement may lead to overinterpretation and overclassification, particularly upgrading of lesions from Bosniak II or IIF to Bosniak III. For this reason, CEUS should be interpreted in correlation with CECT and MRI, especially in intermediate or suspicious lesions and before referral for urological treatment. At present, CEUS should be regarded primarily as a complementary and problem-solving modality rather than as a standalone procedure determining invasive management (2,5,18–21,30,35–39).

Quantitative CEUS, including TIC parameters, remains a promising but insufficiently standardized research field. Available data suggest potential value in quantitative assessment of enhancement, septal and wall thickness and vascularized lesion volume. However, standardized protocols, validated cut-off values and large prospective multicenter studies are still lacking (44,45).

Future research should focus on standardization of CEUS protocols, harmonization of CEUS-adapted Bosniak criteria and prospective validation of qualitative and quantitative enhancement features. The key unresolved question is whether CEUS-Bosniak can become an independently standardized classification system or whether it should remain complementary to CECT and MRI. At the current stage, the safest approach appears to be multimodal assessment of complex renal cystic lesions, integrating B-mode ultrasound, CEUS, CECT and MRI with the clinical context of the patient (1–7,12–23,32–45,52–58).

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