Multiparametric imaging combines the information from different functional imaging
sequences or techniques and is best known from multiparametric MRI in which the information
of a number of different sequences is used to investigate lesions. By combining the
analysis of several structural and functional tissue properties, the characterization
of lesions is much more precise than by just relying on one sequence or technique
only. In fact, the combination of the variety of MRI imaging procedures and sequences
as a “one-shop” procedure resulted in the term “multiparametric”. Multiparametric
MRI is used in daily clinical practice in neuroimaging, liver imaging, musculoskeletal
imaging, breast imaging, prostate imaging, etc. The term ‘multiparametric’ can also
be applied to computed tomography (CT) as it allows functional imaging, 3D-reconstruction
and imaging at different phases after contrast administration. CT has improved the
visualization of the chest, pleural and abdominal cavity and revolutionized trauma
management and plays a fundamental role in the diagnosis of the acute abdomen. Despite
the undisputed strengths of MRI and CT, limitations are obvious: radiation exposure,
foreign bodies with contraindication for MRI, patient movement with and without injection
of contrast media, high cost and limitations of availability and, above all, impossibity
to us CT and MRI on the bedside and directly “at the point of need”, claustrophobia
in a significant proportion of patients, sedation in pediatric use and others [1]
[2]. In recent decades, ultrasound imaging has also outgrown the one-dimensionality
of A-Mode and the frequency-dependent high-resolution visualization of morphological
details in B-Mode in several ways: functional processes can be mapped in real time,
structural details displayed in 4 D, and the interaction of structures with the propagation
characteristics of sound waves can be used for qualitative and quantitative analysis
of tissue elasticity in strain and shear wave elastography, fat infiltration on attenuation
imaging and potentially necro-inflammation using shear wave dispersion. Doppler techniques
and contrast-enhanced techniques quantitatively capture blood flow, vascular density
and vascularization patterns in lesions and their surroundings in real-time – with
the highest temporal and spatial resolution [3]
[4]
[5]
[6]. This multitude of information on tissue properties is achieved with lower costs
and lower patient morbidity than by any other imaging modality. In fact, since the
first use of the term ‘multiparametric ultrasound’ (MPUS) [7], years by years more popularity was gained in literature and among scientific societies
active in the field of medical imaging on its use to describe modern ultrasound imaging,
combining various technologies to precisely characterize focal lesions and their interaction
with surrounding parenchyma and combining a multitude of structural and functional
tissue features, perhaps similar to the terminology used in MRI [8]. Since its foundation, the European Federation of Societies for Ultrasound in Medicine
and Biology (EFSUMB) has established a strong tradition of supporting good clinical
practice and in promoting evidence-based medicine [9]
[10]. Considering the high clinical utility of those newer ultrasound techniques, EFSUMB
has published several clinical guidelines, technical reviews, and position papers
on many areas of medical ultrasound including CEUS [11]
[12]
[13]
[14], the analysis of time intensity curves [15], elastographic techniques [5]
[6], but also in interventional ultrasound [16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24] and gastrointestinal ultrasound [25]
[26]
[27]
[28]
[29]
[30]. In light of the increasing number of publications and the need to analyse benefits
and limitations, as well as to standardize the use of multiparametric ultrasound (MPUS),
EFSUMB has decided to launch the first MPUS guidelines for “small parts” (thyroid,
testis, breast) and to proceed with guidelines on the pancreatic application of MPUS. Guidelines
on the application of MPUS to the liver have already been published by the World Federation
for Ultrasound in Medicine and Biology (WFUMB) in close cooperation with EFSUMB [31]
[32].
All the applications will be presented in comparison with other imaging modalities
that are necessary to address the various pathological entities. Together with the
recently published PoCUS guideline [33], EFSUMB’s multiparametric guidelines are the first to be fully compliant with the
EFSUMB Policy Document Development Strategy developed in 2019 [34] and following a systematic evidence-based approach. They have been established in
3 phases, which are guided by the guideline expert panel steering committee:
-
Phase 1: Defining clinically relevant key questions by the guideline expert panel,
formation of small task force groups from the expert panel for each individual key
question, systematic literature search on these key questions and creation of evidence
tables
-
Phase 2, carried out in small task force groups formed for each individual key question:
critical review of the results of the systematic literature search based on evidence
tables, drafting statements/recommendations, assigning levels of evidence and grading
the strength of recommendation, preparing explanatory comments
-
Phase 3: Structured expert panel consensus process including discussion, modification
and approval of recommendations and statements by voting.
A comprehensive and systematic literature search using the PRISMA methodology [35] formed the foundation of all MPUS guidelines and consisted of defining specific
search strategies in different online databases to retrieve eligible studies. For
this reason, 2 scientific librarians were included in the expert group. The key questions
were prepared in a PICO format, and for each key question a search strategy was developed
based on appropriate search term combinations. The databases MEDLINE (PubMed), CENTRAL,
and EMBASE were used to search for full-text articles published in English language
in the last 3 decades (systematic review, meta-analysis, guideline, clinical study,
clinical trial) matching the predefined search term (PubMed: MeSH term) combinations.
Case studies (with fewer than 10 cases), editorials, comments, letters and abstracts
without full-text paper have been excluded.
In phase 2a thorough and systematic literature search related to the topics and related
key questions was performed. The results were assigned to the task forces in order
to critically review the selected evidence according to the defined search strategy
with regard to its methodological quality. For each key question, the process of evidence
selection with inclusions and exclusions according to the defined criteria was displayed
in a PRISMA flowchart and in an evidence table. The last step was to draft a statement
or recommendation for each key question – based on the results of the systematic literature
search and evidence evaluation. Levels of evidence and strength of recommendation
(the latter applicable only for recommendations) were assigned, and comments explaining
the recommendations and shortly summarizing their evidence basis will be prepared.
Comments briefly summarize and critically evaluate the available evidence and their
clinical relevance and applicability. Recommendations give specific and precise advice
as to which a particular procedure or technique, and under what circumstances, should
be applied or not applied. Statements describe the results of an evidence search related
to a particular key question without giving action advice. Phrasing follows the „guideline
language“ described in the position paper on EFSUMB policy documents [34]. The quality of evidence was assessed using the 2011 Oxford Centre for Evidence-Based
Medicine (OCEBM) Levels of Evidence (LoE) which are based on the assessment of type
and quality of study design. LoE range from 1–5 (1 being the highest, based on consistent
results of systematic reviews and 5 the lowest, based on expert consensus and good
clinical practice). Downgrading of the LoE is possible because of limitations in study
quality or inconsistency between study results, indirectness of evidence with regard
to the key question, or small effect size. Conversely, LoE upgrade is possible if
the clinical effect is large [34]. Based on assigning a LoE and considering benefits in relation to possible harm
of any suggested or recommended intervention, patients’ preferences, resource implications,
feasibility/availability and equity issues, a strong or weak Grade of Recommendation
(GoR) was allocated to each recommendation using the Grading of Recommendations Assessment,
Development and Evaluation (GRADE, 2008) approach [34].
Approximately 4 weeks prior to the consensus meeting the drafts (recommendations/statements
and related comments and evidence tables) of each task force was send out to all members
of the whole expert panel for critical evaluation. At the consensus meetings the prepared
recommendations and statements, the underlying evidence and unresolved or controversial
issues were presented by the task force for discussion. A structured consensus process,
moderated by the steering group, was used to reach agreement on the recommendations
and statements prepared by the respective task force group or on alternative phrasings
proposed by other expert panel members. Finally, the expert panel voted on each recommendation
and statement. A recommendation or statement was approved if > 75 % of voting members
are in agreement (strong consensus: ≥ 95 % of votes; broad agreement: > 75–95 % of
votes). In case of failure to gain > 75 % agreement for the primary or a rephrased
or alternative recommendation, the lack of consent on this particular key question
was recorded in the text of the guideline.
With its guideline project on MPUS, EFSUMB aims to contribute to an evidence-based
and standardized use of the multiparametric ultrasound approach to the diagnosis of
thyroid, testis and breast pathologies. Through the integration of modern ultrasound
techniques complementary to B-mode ultrasound in diagnostic algorithms and the weighted
inclusion of different structural and functional features of a given lesion in the
diagnosis, the rate of false-negative and false-positive diagnostic results may be
reduced – and thus unnecessary invasive diagnostics or therapies can be avoided in
clinical practice. However, consideration of clinical pre-test probabilities, awareness
of the limitations of MPUS technologies, knowledge of alternative imaging modalities,
the training required for the professional use of MPUS, the experience required to
evaluate results and excellent quality documentation are critical prerequisites for
the success of multiparametric ultrasound diagnostics [36].
