Diffusion-weighted MR imaging of the rectum: Clinical applications

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Critical Reviews in Oncology/Hematology xxx (2014) xxx–xxx

Diffusion-weighted MR imaging of the rectum: Clinical applications Truong Luong Francis Nguyen a,∗ , Philippe Soyer b , Paul Fornès c , Pascal Rousset d , Reza Kianmanesh e , Christine Hoeffel a a

c

Department of Radiology, Hôpital Robert Debré, Avenue du Général Koenig, 51092 Reims Cedex, France b Department of Radiology, Hôpital Lariboisière, 2 rue Ambroise Paré, 75010 Paris, France Department of Histopathology and Cytology, Hôpital Robert Debré, Avenue du Général Koenig, 51092 Reims Cedex, France d Department of Radiology, Hôpital Hôtel Dieu, 1 place du Parvis de Notre Dame, 75181 Paris Cedex 4, France e Department of Abdominal Surgery, Hôpital Robert Debré, Avenue du Général Koenig, 51092 Reims Cedex, France Accepted 22 July 2014

Contents 1. 2.

3.

Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Technical background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Diffusion-weighted MR imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.1. Basic principles of diffusion-weighted MR imaging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.2. Diffusion-weighted MR imaging technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.3. Qualitative analysis with diffusion-weighted MR imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.4. Quantitative analysis with diffusion-weighted MR imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Rectal DW-MR imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Rectal diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Normal rectal wall . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Inflammatory processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Primary rectal cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.1. Detection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.2. Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.3. Primary rectal cancer staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.4. Response to neoadjuvant treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4. Lymph nodes evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5. Rectal cancer: Pelvic recurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.6. Future trends and conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Biographies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00

Abstract Dramatic advances in image quality over the past few years have made diffusion-weighted magnetic resonance imaging (DW-MRI) a promising tool for rectal lesion evaluation. DW-MRI derives its image contrast from differences in the motion of water molecules between tissues. Such imaging can be performed quickly without the need for the administration of exogenous contrast medium. The technique yields qualitative and quantitative information that reflects changes at a cellular level and provides information about tumor cellularity and the integrity of cell membranes. The sensitivity to diffusion is obtained by applying two bipolar diffusion-sensitizing gradients to a standard T2-weighted spin echo sequence. The diffusion-sensitivity can be varied by adjusting the “b-factor”, which represents the gradient duration, ∗

Corresponding author. Tel.: +00 33 3 26 78 42 16; fax: +00 33 3 26 78 84 77. E-mail address: [email protected] (T.L.F. Nguyen).

http://dx.doi.org/10.1016/j.critrevonc.2014.07.002 1040-8428/© 2014 Elsevier Ireland Ltd. All rights reserved.

Please cite this article in press as: Nguyen TLF, et al. Diffusion-weighted MR imaging of the rectum: Clinical applications. Crit Rev Oncol/Hematol (2014), http://dx.doi.org/10.1016/j.critrevonc.2014.07.002

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gradient amplitude and the time interval between the two gradients. The higher the b-value, the greater the signal attenuation from moving water protons. In this review, technical considerations relatively to image acquisition and to quantification methods applied to rectal DW-MRI are discussed. The current clinical applications of DW-MRI, either in the field of inflammatory or neoplastic rectal disease are reviewed. Also, limitations, mainly in terms of persistent lack of standardization or evaluation of tumoral response, and future directions of rectal DW-MRI are discussed. The potential utility of DW-MRI for the evaluation of rectal tumor response is on its way to being admitted but future well-designed and multicenter studies, as well as standardization of DW-MRI, are still required before a consensus can be reached upon how and when to use DW-MRI. © 2014 Elsevier Ireland Ltd. All rights reserved.

Keywords: Apparent diffusion coefficient; Rectum; Diffusion-weighted imaging; Lesion detection; Tumor staging; Inflammation

1. Introduction In the last twenty years, diffusion-weighted magnetic resonance imaging (DW-MRI) has been widely used in neuroimaging whereas its applications within the abdomen are relatively recent due to the availability of newer acquisition techniques that are less sensitive to bowel peristalsis and respiratory movements [1,2]. Since that time, a growing number of studies have demonstrated the usefulness of this method in both the detection and characterization of abdominal lesions, in the oncologic field but also in that of inflammatory bowel diseases. MR imaging is the most accurate imaging modality for evaluating the pelvis, and rectal disease is one of the areas in which clinical research and applications of DW-MRI are numerous. Early publications concerning application of DW-MRI to rectal disease mainly dealt with evaluation of tumor response to treatment [3–6]. Since then, rectal DW-MRI has become a feasible option and several groups have confirmed early encouraging results in the area of rectal disease detection [7–9] or tumoral response evaluation [3,8,10–20]. Recent guidelines for rectal cancer imaging even recommend DW-MRI as part of a standard MR imaging protocol for preoperative restaging of rectal cancers after neoadjuvant chemoradiotherapy (CRT) [21]. However, despite promising perspectives, there is still not any consensus for routine use in terms of DW-MRI protocols, data interpretation and specific indications. A particular advantage of DW-MRI is that it may be useful in patients in whom intravenous administration of gadolinium-based contrast agents is contraindicated. Moreover, DW-MRI sequences can be added to the imaging protocol without significantly increasing overall acquisition time, with a mean time of around 5 min while total pelvic MR examination is approximately 25 to 30 min. Optimization of MR pulse sequences is a critical issue in DW-MRI of the rectum because image quality and diagnostic capabilities greatly depend on imaging protocols. Differences in equipment and lack of standardization among institutions are responsible for variations in results among published studies. This article presents a comprehensive overview of the various DW-MRI protocols that can be used for investigate rectal diseases and their clinical applications, discusses its

limitations and presents the more promising future trends in DW-MRI of the rectum.

2. Technical background 2.1. Diffusion-weighted MR imaging 2.1.1. Basic principles of diffusion-weighted MR imaging Diffusion-weighted MR imaging is a technique that reflects microscopic water diffusion inside a voxel, using a pair of strong diffusion gradients. In the body, water molecules movements encounter different obstacles (cell membrane, proteins, macromolecules, fibers. . .), which vary depending on certain pathological changes (intracellular cytotoxic edema, cell lysis, abscess, hypercellular tumor. . .). Approximately, we can consider that it is mainly the extracellular water that is explored in diffusion imaging. The movements of water molecules can be free (as cerebral spinal fluid, CSF) or restricted (by cell membranes, macromolecules, fibers. . .), in all directions in space (isotropic diffusion) or preferentially in a particular direction (anisotropic diffusion) as in nerve fibers.

2.1.2. Diffusion-weighted MR imaging technique The imaging sequence used for measuring water diffusion [22,23] is a T2-weighted spin echo sequence consisting of a 90◦ radiofrequency (RF) pulse followed by a 180◦ RF pulse. The diffusion-weighting results from the application of a dephasing gradient before the 180◦ RF pulse and of a symmetric rephasing gradient after the 180◦ RF pulse. The moment of latency between the two gradients is part of the b factor and represents the time left to the protons to move freely [24]. When water molecules are static because the tissue is highly cellular such as in tumors, the effect of the dephasing gradient is cancelled out by the second, rephasing, gradient, and the T2 signal is sustained. When the water molecules are able to move because the surrounding tissue is less dense, the mobile molecules will not be fully rephased leading to a decreased T2 signal intensity. This phenomenon is illustrated in Fig. 1.

Please cite this article in press as: Nguyen TLF, et al. Diffusion-weighted MR imaging of the rectum: Clinical applications. Crit Rev Oncol/Hematol (2014), http://dx.doi.org/10.1016/j.critrevonc.2014.07.002

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Fig. 1. This schematic drawing illustrates the impact of diffusion-weighted sequence on water molecules in a highly cellular environment (static water molecules) or in a less restricted environment (water moving molecules). The height of the triangle represents the intensity of the resulting T2 signal.

2.1.3. Qualitative analysis with diffusion-weighted MR imaging Small b values, i.e. 50–100 s/mm2 will result in signal loss in highly mobile water molecules such as what happens with vessels. This is because the water molecules will have moved quickly over long distance by the time the rephasing gradient is applied, and consequently will not regain their original phase information after application of the rephasing gradient. The resulting images are referred to as “black-blood” images due to the signal loss in the fast-flowing blood within vessels. Because water movement in highly cellular tissues is restricted, the water molecules within such tissue retain their signal even at high b values (500–1000 s/mm2 ). This explains why highly cellular tissues such as tumor, brain, spinal cord, normal lymphatic tissue, bowel mucosa etc. appear persistently bright on diffusionweighted images, even at high b values DW-MRI may thus be assessed qualitatively by observing the relative attenuation of signal intensity on images obtained at various b values. It is noteworthy that the relative contribution of T2 signal intensity to DW-MR images may lead to some misinterpretation. For example, simple cysts that have a long relaxation time may appear with high signal intensity on both low and high b value images, but also on ADC maps. This effect can thus result in misinterpretation for a tumor for example if high b value images are viewed without cross-reference to the corresponding ADC maps. Unlike a cyst, a region with truly restricted diffusion will demonstrate low signal intensity on the ADC map.

2.1.4. Quantitative analysis with diffusion-weighted MR imaging ADC corresponds to the slope of the signal decay using a logarithmic scale according to the b values used [25,26]. The steeper the slope, the quicker the ADC is high (e.g. CSF presents a high ADC). Quantitative analysis of diffusionweighted imaging findings can be performed only if at least two b values are used. Of course, the fit can be improved by increasing the number of b values to reduce the error in ADC calculation but it will increase scanning time. The optimal b values for tissue characterization depend on the tissue (organ) being evaluated. By drawing regions of interests on the parametric maps, the ADCs of different tissues can be derived. The analysis of the ADC is an automated process that is available on most scanners or workstations. Areas of restricted diffusion in highly cellular areas show low ADC values compared with less cellular areas that return higher ADC values. 2.2. Rectal DW-MR imaging Some requirements are needed for DW-MRI of the rectum. Patients are generally imaged in supine position, using either a dedicated cardiac [16] coil or a phased-array torso or body coil [10,27]. MR units working at 3-Teslas (T) are becoming more commonly used for MR imaging of the rectum. In theory, the increased signal-to-noise ratio (SNR) provided by 3 T MR scanner, with parallel imaging techniques, makes possible an increase in either the spatial resolution or image quality of

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ADC maps [12,19]. Actually, in current practice, the advantage of the increased SNR at 3 T is generally counterbalanced by higher susceptibility artifacts. At the present time, there are no studies in the literature comparing DW-MRI of the rectum at 1.5- and 3-T in a same group of patients. Details relative to the way DW-MRI examinations are being performed are listed in Tables 1 and 2. A few authors advocate the use of bowel preparation based on rectal suppository laxatives [10,12,16]. Several studies have reported the use of intravenous administration of spasmolytic agents to reduce bowel peristalsis, which may be particularly useful at 3 T MR imaging [11–13,16,18]. When performing MR imaging for rectal tumor evaluation, some groups perform luminal distension, using mainly ultrasonographic gel [13,14,28] or tap water [18]. Although the European Recommendations from the European society of gastrointestinal and abdominal radiology (ESGAR) do not recommend routine rectal filling [21], some groups somehow suggest that filling might be helpful to reduce susceptibility artifacts during DW-MRI of the rectum [10,28]. Whereas intravenous gadolinium administration is not recommended for rectal tumor MR evaluation [21], gadolinium chelates are generally used for anorectal inflammatory disease evaluation [29]. In case of gadolinium administration, although no study has specifically studied rectal disorders, some authors have suggested that DW-MRI should be acquired before gadolinium-enhanced MR sequences because gadolinium chelates might reduce calculated ADC values of lesions and slightly affect image quality [30,31]. Conversely, others have not found any significant change of the ADC values of focal hepatic lesions when DW-MRI was performed after gadolinium injection [32]. The use of high-resolution T2-weighted single-shot-echo technique in the axial plane is uniformly recommended. Some studies have reported the use of parallel imaging with generalized autocalibrating partially parallel acquisition (GRAPPA) allowing slight reduction in acquisition time [8,18]. The impact of respiratory movements on image quality of the rectum is limited and free-breathing techniques are thus commonly used [8–11,13,18,28]. High b values (between 800 and 1000 s/mm2 ) are generally used and at least 3 b values are applied in recent studies [12,15,17]. Slice thickness usually ranges between 3 mm and 5 mm with a gap of 0 to 1 mm (Table 1). Total acquisition time of diffusion-weighted MR sequences ranges between 2 min to 10 min (Table 2). As far as quantitative measurements of the apparent diffusion coefficient (ADC) are concerned, a study has shown that rectal tumor ADC values and interobserver variability are highly dependent on the methods of region of interest (ROI) analysis [33]. Moreover this study, as well as another one, has demonstrated that ADC measurements obtained from the whole tumor volume, although time-consuming, are more reproducible than those obtained from single slice or small sample measurements [33,34]. Conversely, Monguzzi et al. found no significant interobserver variability for ADC

Fig. 2. Complex fistula in ano in a 32 year-old male patient with Crohn’s disease. Fusion MR image (a) between high b value diffusion-weighted MR axial image and the corresponding T2 fat-suppressed weighted MR image (b) optimally depicts the complex fistula and its extent in the right ischioanal fossa (arrowhead).

measurements using one-slice technique, with two readers performing three measurements on three different sections and using T2-weighted MR images as an adjunct for a precise localization of the ROI on the tumor [28]. ROIs may indeed be drawn hand-free along the border of the high signal area, on the ADC map based on the corresponding axial T2 weighted images, or on the b 1000 images [35] or on low b DW-MR images [8]. ROIs are drawn in order to cover the entire tumor area of each consecutive tumor containing slice [12,13,15,17–19,28,35–37] with mean ADC and standard deviation (SD) obtained for each slice or placed on a single slice containing the largest available tumor area [8]. ADC min is determined as the lowest ADC value among all ROIs in each tumor, whereas ADC max is the highest and mean ADC the average of ADC values. Some authors calculate mean ADC from a sample of three round or oval

Please cite this article in press as: Nguyen TLF, et al. Diffusion-weighted MR imaging of the rectum: Clinical applications. Crit Rev Oncol/Hematol (2014), http://dx.doi.org/10.1016/j.critrevonc.2014.07.002

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Magnet strength (T)

Clinical indications

Preparation/ spasmolytic

Luminal distension

b values (s/mm2 )

Slice thickness/gap (mm)

TR/TE (ms)

Soyer et al. [8]

1.5

No/no

No

0, 500, 1000

5/1

3900/91

Ichikawa et al. [9]

1.5

No/no

Gel

0, 1000

4/0

Kim et al. [10]

1.5

Yes/yes

Gel

0, 1000

5/1

8000–10,000/73.273.4 8000/85.2

Sun et al. [11]

1.5

No/yes

No

0, 1000

5/1

6000/66.6

Song et al. [12]

3

Yes/yes

Gel

0, 100, 800, 1000

3/1

2820/70

Kim et al. [13]

1.5

Yes/yes

Gel

0, 600, 1000

5/1

8000/85.2

Jung et al. [14]

3

No/no

N.S.

0, 500, 1000

4/1

2100–3308/85

Curvo-Semedo et al. [15]

1.5

No/no

No

0, 500, 1000

5/0

4829/70

Park et al. [16]

3

Yes/yes

Gel

0, 100, 800, 1000

3/1

2820/70

Lambrecht et al. [17]

1.5

No/no

No

0, 50, 100, 500, 750, 1000

4/0

4500/83

Kim et al. [18]

3

No/yes

Water

0, 300, 1000

5/1

6600/79

Intven et al. [19]

3

N.S.

N.S.

0, 200, 800

4/0

7600/63

Lambregts et al. [27]

1.5

No/no

No

0, 500, 1000

N.S.

4829/70

Monguzzi et al. [28]

1.5

No/no

Gel

0, 1000

6/6

3000/74

Lambregts et al. [33]

1.5

No/no

N.S.

0, 500, 1000

N.S.

4829/70

Barbaro et al. [36]

1.5

N.S.

Gel

0, 600, 1000

4/0.5

>8000/minimum

Hori et al. [41] Nguyen et al. [42]

1.5 1.5

LARC: Detection or primary tumors with free-breathing DW SSEP MRI using parallel imaging (GRAPPA 2) and high b value High-B-value DW-MRI for detection of colorectal cancer LARC: DW-MRI for evaluation of tumor response to CRT LARC: DW-MRI for early detection of tumor histopathologic downstaging after CRT LARC: DW-MRI in the detection of viable tumor: comparison with T2WI and PET/CT imaging LARC: ADC for evaluating tumor response to CRT Predicting response to neoadjuvant CRT in LARC: DW-MRI at 3 T LARC: assessment of CR to CRT-conventional MR volumetry versus DW-MRI LARC: DW-MRI for predicting tumor clearance of the mesorectal fascia after CRT LARC: DW-MRI for prediction and early assessment of response to CRT LARC: Comparison of DW-MRI and MR volumetry for evaluation of early treatment outcomes after CRT LARC: DW-MRI for pathological response prediction after CRT Locally recurrent rectal cancer: Value of MRI and DW-MRI for the diagnosis LARC: ADC mapping for prediction of tumor response after CRT LARC: ADC measurements for nodal staging after CRT LARC: DW-MRI for monitoring of response to CRT DW-MRI for the diagnosis of fistula in ano DW-MRI for diagnosis of Pelvic Abscesses

No/no No/no

No No

0, 800 0, 500, 1000

5/7 4/N.S.

3000–10,000/70–80 3900/80

Note: mm indicates millimeters; N.S. indicates that the information was not stated in the paper; T means Tesla; Luminal distension: ultrasound gel or tap water; NSA indicates the number of signal averages; LARC means locally advanced rectal cancer; DW-MRI means diffusion-weighted magnetic resonance imaging; CRT means chemoradiotherapy; ADC means apparent diffusion coefficient; CR means complete response; SSEP means single-shot echo-planar.

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Please cite this article in press as: Nguyen TLF, et al. Diffusion-weighted MR imaging of the rectum: Clinical applications. Crit Rev Oncol/Hematol (2014), http://dx.doi.org/10.1016/j.critrevonc.2014.07.002

Table 1 Details of rectal DW-MRI examination throughout the literature—Part 1.

5

Number of slices

Matrix size (mm)

Voxel size (mm)

FOV (mm)

Acquisition time

ROI

Soyer et al. [8]

LARC: detection or primary tumors with free-breathing DW SSEP MRI using parallel imaging (GRAPPA 2) and high b value High-b-value DW-MRI for detection of colorectal cancer LARC: DW-MRI for evaluation of tumor response to CRT LARC: DW-MRI for early detection of tumor histopathologic downstaging after CRT LARC: DW-MRI in the detection of viable tumor: comparison with T2WI and PET/CT imaging LARC: ADC for evaluating tumor response to CRT Predicting response to neoadjuvant CRT in LARC: DW-MRI at 3 T LARC: assessment of CR to CRT-conventional MR volumetry versus DW-MRI LARC: DW-MRI for predicting tumor clearance of the mesorectal fascia after CRT LARC: DW-MRI for prediction and early assessment of response to CRT LARC: comparison of DW-MRI and MR volumetry for evaluation of early treatment outcomes after CRT LARC: DW-MRI for pathological response prediction after CRT Locally recurrent rectal cancer: value of MRI and DW-MRI for the diagnosis LARC: ADC mapping for prediction of tumor response after CRT LARC: ADC measurements for nodal staging after CRT LARC: DW-MRI for monitoring of response to CRT DW-MRI for the diagnosis of fistula in ano DW-MRI for diagnosis of pelvic abscesses

25

182 × 192

2.2 × 2.0 × 5.0

300 × 400

2 mn

Entire tumor

60

128 × 64

N.S.

N.S.

5 mn

N.S.

26

160 × 160

N.S.

300 × 300

2 mn 8 s

>4 mm2

3–10 on tumor

128 × 128

N.S.

360 × 360

2 mn 40 s

>20 voxels

N.S.

104 × 100

N.S.

360 × 360

1 mn 53 s

Entire tumor

26

160 × 160

N.S.

300 × 300

4 mn 54 s

Entire tumor

N.S.

128 × 128

N.S.

250 × 250

4 mn

Entire tumor

50

N.S.

2.5 × 3.11 × 5.0

N.S.

10 mn 37 s

Entire tumor

N.S.

104 × 100

N.S.

360 × 360

1 mn 53 s

Entire tumor

34

128 × 128

N.S.

380 × 380

N.S.

44

192 × 156

N.S.

260 × 320

2 mn

Entire tumor or solid portion Entire tumor

N.S.

132 × 120

N.S.

N.S.

4 mn 08 s

Entire tumor

50

N.S.

2.5 × 3.11 × 5.0

N.S.

10 mn 37 s

N.S.

12

240 × 256

N.S.

380*

1 mn 30 s

Entire tumor

50

N.S.

2.5 × 3.11 × 5.0

N.S.

10 mn 37 s

Entire node

N.S.

128 × 128

N.S.

400 × 400

N.S.

Entire tumor.

N.S. N.S.

128 × 128 128 × 128

N.S. 2×2×4

320 × 500 250 × 250

2–4 mn 4 mn 16 s

N.S. At least 2 thirds of the necrotic part

Ichikawa T. et al. [9] Kim S.H. et al. [10] Sun et al. [11]

Song et al. [12]

Kim et al. [13] Jung et al. [14] Curvo-Semedo et al. [15]

Park et al. [16] Lambrecht et al. [17] Kim et al. [18]

Intven et al. [19] Lambregts et al. [27] Monguzzi et al. [28] Lambregts et al. [33] Barbaro et al. [36] Hori et al. [41] Nguyen et al. [42]

Note: mm indicates millimeters; mn indicate minutes; s indicates seconds; N.S. indicates that the information was not stated in the paper; FOV: field of view; ROI: region of interest; SSE: single shot fast spin echo; Fat Sat: fat saturation; DWIBS: diffusion-weighted whole-body imaging with background body signal suppression; SPAIR: spectral attenuated inversion recovery; LARC means locally advanced rectal cancer; DW-MRI means diffusion-weighted magnetic resonance imaging; CRT means chemoradiotherapy; ADC means apparent diffusion coefficient; R means complete response; SSEP means single-shot echo-planar. * rFOV = 80.

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Table 2 Details of rectal DW-MRI examination throughout the literature—Part 2.

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shaped ROIs placed within the most solid tumor part [35,38] (Table 2). ROI measurement should parallel those made in nuclear medicine (SUV measurement) to calculate ADC value and homogenize practices to make interstudy comparison easier [37].

3. Rectal diseases 3.1. Normal rectal wall Soyer et al. have studied the ADC values of 31 patients without rectal malignancies and those of 31 patients with rectal adenocarcinoma examined with diffusion-weighted MR imaging at 1.5 T using three b-values of 0, 500 and 1000 mm2 /s [8]. Despite highly statistically significant differences in mean ADC values between rectal adenocarcinomas and normal rectal wall, they found some degrees of overlap between the two groups. Using a threshold value of less than 1.240 × 10−3 mm2 /s, they found only two cases of falsepositive findings [8]. 3.2. Inflammatory processes DW-MRI has been reported to be a reliable tool for detecting colonic inflammation in inflammatory bowel disease [7,39–44]. In a prospective series of 96 patients who underwent DW-MRI colonography without any oral nor rectal bowel preparation, colonic and rectal inflammation were ideally detected in Crohn’s disease and ulcerative colitis, with high signal intensity on DW-MR images that correlated with endoscopic assessment of inflammation in both diseases, although even better in ulcerative colitis. It has also been reported that the use of DW-MRI may be of some help as an adjunct to T2-weighted MR sequences, particularly in patients that cannot receive intravenous gadolinium-chelates for the detection and depiction of extent of anorectal fistulae, particularly for inexperienced readers [41] (Fig. 2). The use of DW-MRI also allows optimal depiction not only of inflammatory and/or infectious rectal wall disease but also of mesorectal or pelvis abscesses that may be associated with rectal infection or pelvic inflammatory disease [42] (Fig. 3). 3.3. Primary rectal cancer 3.3.1. Detection Although rectal cancer detection generally relies on clinical examination and endoscopy rather than on imaging, there may be some cases for which DW-MRI helps locate rectal

Fig. 3. Inflammatory pelvic disease in a 22 year-old woman. Axial T2weighted MR images (a) show mesorectal small abscesses (black arrows) that are ideally visualized on high b value (b = 1000) diffusion-weighted

MR images (b) as high signal intensity small collections standing out on the suppressed background (white arrows). ADC map (c) show corresponding areas displaying restricted diffusion and thus low signal intensity (white arrows).

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tumor during primary staging, for example in case of a small rectal tumor whose location is not mentioned by the referring physician. It has indeed been shown that the addition of DWMRI to conventional T2-weighted imaging provides better detection of rectal cancer [8,9,45] (Fig. 4). Rao et al. have demonstrated in a series of 45 patients with rectal cancer and 20 without rectal cancer that the sensitivity for detection of rectal cancer increased from 82–84% to 93–96%, the specificity from 85–90% to 95–100%, the positive predictive value (PPV) from 92–95% to 98–100% and the negative predictive value (NPV) from 68–72% to 86–91% for both readers with the addition of DW-MRI to T2-weighted MR imaging [45]. It is not however recommended to add diffusion-weighted MR sequences to MR protocol for primary staging [21] although these sequences are an adjunct to T2-weighted MR sequences for tumor detection. 3.3.2. Characterization In their study, Soyer et al. found that adenocarcinomas had a significantly lower ADC value 1.036 × 10−3 ± 0.107 × 10−3 mm2 /s; range (mean −3 0.827 × 10 –1.239 × 10−3 ) than rectal wall of control subjects [8]. Curvo-Semedo et al. found similar values in a series of 50 rectal tubular adenocarcinomas with a mean ADC value of 1.069 ± 0.162 × 10−3 mm2 /s. They also reported that lower ADC values were associated with a more aggressive tumor profile [38]. Indeed, the pre treatment mean tumor ADC value differed significantly in their series between the different groups depending on histological differentiation grades (i.e. 0: poorly differentiated, (1) poorly to moderately differentiated, (2) moderately differentiated, (3) moderately to well differentiated, (4) well differentiated). Tumors that were less well differentiated indeed showed relatively low ADC values (p = 0.025). Moreover, pretreatment mean ADC value was significant lower for tumors invading mesorectal fascia (MRF) or tumors with node positive disease. Among rectal adenocarcinomas, it is noteworthy that mucinous adenocarcinomas, characterized by the presence of mucoid pools and a more aggressive behavior, have significantly higher ADC values and lower signal intensity in DW-MR images, with mean reported ADC values of 1.49 ± 0.34 × 10−3 mm2 /s for mucinous carcinomas and 0.80 ± 0.15 × 10−3 mm2 /s for tubular adenocarcinomas [46] (Fig. 5). To our knowledge, no studies have been performed to determine whether ADC values differed significantly between rectal tubular adenocarcinomas and other adenocarcinomatous tumor types (villous for example) or other non adenocarcinomatous tumor types, i.e. lymphoma, carcinoid tumor, gastrointestinal stromal tumors (GIST) etc (Fig. 6). To date, there is no threshold of ADC value allowing characterization of tubular rectal adenocarcinomas or other tumor types, which still relies on biopsy and histology.

Fig. 4. Axial T2-weighted MR image (a) hardly demonstrates a small T2 middle rectal tumor in a 66 year-old man (black arrow), which is much more conspicuous on axial high b value (b = 1000) MR image ((b) white arrow).The tumor displays relatively low ADC on the corresponding ADC map ((c) white arrow).

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Fig. 5. Mucinous low rectal adenocarcinoma in a 85 year-old man, displaying high signal intensity on T2-weighted MR images ((a) black arrows), high signal intensity on high b value diffusion-weighted MR images ((b) white arrows), and no restriction of diffusion on the ADC map with an ADC value of 1.915 × 10−3 mm2 /s ((c) black arrows).

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Fig. 6. Carcinoid upper rectal tumor in a 67 year-old male on axial T2weighted MR image ((a) black arrows) and adjacent tumoral mesorectal deposit ((a) black arrowheads) displaying high signal intensity on high (b = 1000) b value DW-MR image ((b) white arrow and arrowheads), and exhibiting an ADC value in the range of that of tubular adenocarcinomas, i.e. 0.997 × 10−3 mm2 /s on the ADC map ((c) black arrow and arrowheads).

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Fig. 7. Axial MR images of a low rectal cancer in a 64 year-old patient. Axial T2-weighted (a), high b value (b = 1000) (b) DW-MR images and ADC map of the tumor (c) obtained before chemoradiation therapy show a small middle rectal T3 tumor (arrow). Axial T2-weighted (d) MR image obtained at the level of

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3.3.3. Primary rectal cancer staging The role of DW-MRI in primary rectal cancer staging is still debated. As far as nodal staging is concerned, DWMRI does improve lymph node detection [47–49] but, when used alone, is not reliable for differentiating between benign and malignant lymph nodes [33,50]. In our experience and accordingly to the ESGAR’s guidelines for rectal tumor imaging [21], there is no evidence so far that DW-MRI improves rectal primary staging. Whole-body DW-MRI has been suggested as a more timeand cost-effective imaging modality for the staging of a number of oncologic diseases and a few authors have reported on the performances of whole-body MRI for the detection of recurrence in patients with colorectal cancer [51] or on its cost-effectiveness for staging patients with rectal cancer [52]. However, to our knowledge, no published study exists so far on the use of whole-body DW-MRI as a single staging modality in colorectal cancer [53]. 3.3.4. Response to neoadjuvant treatment There is currently a trend to a paradigm shift from a standard treatment for all patients toward a minimally invasive approach in patients who have responded favorably to neoadjuvant treatment. Response evaluation of locally advanced rectal cancers (LARC) after CRT is thus emerging as a critical issue. In this regard, DW-MRI has been investigated as a new method that could improve selection of patients who may be eligible to organ saving treatments [3,10,12,13,16,17,19,36]. This is because DW-MRI has been reported as being superior to conventional MR imaging for detecting or excluding presence of residual viable tumor within the irradiated fibrotic tumor bed [27,54–56]. 3.3.4.1. Prediction of tumor response. Results concerning the impact of pre-radiochemotherapy ADC values on prediction of rectal tumoral response to neoadjuvant treatment are somewhat conflicting and are detailed in Table 3. Some authors have suggested that initial ADC values might predict whether patients are likely to respond favorably to treatment or not, as soon as one or two weeks after the onset of the neoadjuvant treatment [11,14,17]. Conversely, others found no difference in the pre-CRT distribution of ADC values between non-responders and responders [13,15,18,28,29]. At the present time, prechemoradiotherapy ADC values cannot be used for definite prediction of rectal tumor response to neoadjuvant treatment. 3.3.4.2. Tumor response evaluation. Studies reporting on the value of tumor ADC measurement after completion of

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CRT provide discrepant results detailed in Table 4. Most authors have reported a significantly higher mean posttreatment ADC value in the complete responder group [10,12,13,19,28,36], whereas others reported that there was no difference in mean ADC values between both the responder and the non responder populations [11,15]. Difficulty in interpreting studies results is often due to the fact that some authors binary categorize the patients in responders and non responders with respect to downstaging [11,17,28,36], whereas others categorize response in pCR or non pCR [10,12,13,15,19]. These discrepancies in terms of results are also related to the difference in the definition of the standard of reference. For example, Sun et al. used the ypTNM staging system [11], while others [14,15,18–20,28,36] chose the tumor regression grade according to Mandard’s classification. Moreover, some studies have included patients with mucinous tumors [10–13,15,16], known as displaying a different behavior with DW-MRI than that of tubular adenocarcinomas, whereas others did not [8,17–19]. Differences in time interval between the MR examination and the onset of CRT may also greatly influence results. Lastly, ADC values differ according to T2, b factor, echo time and other parameters. Normative references for characteristics and ADC values are thus necessary for comparisons. Given the difficulty of implementing ADC measurements in clinical practice, studies have focused on the added value of visual assessment of the high signal intensity of residual tumor on DW-MR images obtained with high b values [16,20]. Most studies showed that the adjunct of DW-MR images to conventional images increased the sensitivity for the detection of residual tumor, resulting in lower degrees of overestimation of tumor in patients with a complete tumor response [10,12,20] (Fig. 7). One main multicenter retrospective study dealing with 120 patients with LARC [20] found that area under the ROC curve (AUC) for identification of a complete tumor response after CRT increased for all readers after addition of DW-MRI, although significantly only for the two less experienced readers. Sensitivity for detecting complete response in their study was somehow only 52–64%, thus showing that presence of residual tumor was still overestimated in a number of cases. Another group [15] found higher degrees of AUCs (0.93) for the assessment of a pCR, pCR being defined as the absolute absence of hyperintense areas within the rectal wall. The same group also evaluated tumor volumetry performed using high b values DW-MR images and found similar performances as those reported before using T2-weighted MR images, both before and after treatment. They thus suggested that post treatment diffusion-weighted MR images are sufficient for volumetric evaluation of the rectal tumor [57,58].

the tumor after chemoradiotherapy and after rectal distension using ultrasound gel shows a small residual area displaying intermediate signal intensity (white arrows). Analysis of high b value diffusion-weighted MR image (e) and ADC map (f) of the tumor after radiochemotherapy at the same level than that of a, b and c does not show any residual high signal intensity, thus suggesting complete response. This complete response that was suggested by diffusion-weighted MR images was confirmed by histopathological examination of the resected specimen.

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Number of patients

Standard of reference

Nonmucinous/ mucinous tumor

Criteria used as an endpoint

ADC for favorable response group (10−3 mm2 /s)

ADC for non favorable response group (10−3 mm2 /s)

Statistical difference

Cutoff ADC value (10−3 mm2 /s)

Cutoff: Se/Sp/accuracy (%)

Cutoff: PPV/NPV (%)

Sun et al. [11] Kim et al. [13] Jung et al. [14] CurvoSemedo et al. [15] Lambrecht et al. [17] Kim et al. [18] Intven et al. [19] Monguzzi et al. [28]

Prospect Retrosp Retrosp Retrosp

37 76 35 50

33/4 74/2 N.S. 54/6

Downstaging Pcr Donwstaging pCR

1.07 ± 0.13 0.85 ± 0.10 0.93 ± 0.09 1.07 ± 0.15

1.19 ± 0.15 0.88 ± 0.14 1.03 ± 0.08 1.10 ± 0.19

p = 0.013 p = 0.4094 p = 0.034 p = 0.61

N.S. 0.91 N.S. <0.97

N.S. 81.8/38.5/44.7 N.S. N.S.

N.S. 18.4/92.6 N.S. N.S.

Retrosp

20

Pathology Pathology Pathology Pathology or clinical evidence Pathology

N.S.

pCR

0.94 ± 0.12

1.19 ± 0.22

p = 0.003

<1.06

100/86/N.S.

75/100

Prospect Prospect

34 59

Pathology Pathology

34/0 Excluded

Downstaging pCR

0.89 0.97

0.91 1.09

p = 0.53 p = 0.010

N.S. <0.97

N.S. 56/86/81

N.S. 42/91

Prospect

31

Pathology

1/30

Downstaging

0.83

0.82

p = 0.273

N.S.

N.S.

N.S.

Notes: N.S. indicates not stated in the paper; Se: sensitivity; Sp: specificity; PPV: Positive predictive value; NPV: Negative predictive value; Acc: accuracy; Prosp: prospective; Retrosp: retrospective; pCR: pathological complete response; CR: complete response.

Table 4 Tumoral response evaluation using ADC measurement of the rectal tumor after completion of CRT. Study

Design

Number of patients

Standard of reference

Nonmucinous/ mucinous tumor

Criteria used as an endpoint

ADC for favorable group (10−3 mm2 /s)

ADC for non favorable group (10−3 mm2 /s)

Statistical difference

Cut-off ADC (10−3 mm2 /s)

Cutoff: Se/Sp/accuracy (%)

Cutoff: PPV/NPV (%)

Kim et al. [10] Sun et al. [11] Song et al. [12] Kim et al. [13] CurvoSemedo et al. [15] Intven et al. [19] Monguzzi et al. [28] Barbaro et al. [36]

Retrosp Prosp Retrosp

40 37 50

Pathology Pathology Pathology

34/6 33/4 49/1

pCR Downstaging pCR

1.62 ± 0.36 1.30 ± 0.09 1.55 ± 0.49

1.04 ± 0.24 1.28 ± 0.13 0.93 ± 0.18

p < 0.0001 p = 0.558 p < 0.0001

>1.20 N.S. >1.045

100/79/85 N.S. 75/100/78

65/100 N.S. N.S.

Retrosp Retrosp

76 50

74/2 44/6

pCR pCR

1.43 ± 0.10 1.39 ± 0.24

1.14 ± 0.18 1.45 ± 0.28

p < 0.0001 p = 0.48

>1.30 >1.41

100/84.6/86.8 N.S.

52.4/100 N.S.

Prosp

59

Pathology Pathology or Clinical evidence Pathology

pCR

1.46 (1.22–1.65)

1.35 (1.01–1.88)

p = 0.047

N.S.

N.S.

N.S.

Prosp

31

Pathology

N = 3: excluded 30/1

Downstaging

1.42

1.25

p = 0.0042

>1.294

86/67/N.S.

87/67

Prosp

62

Pathology

N.S.

Downstaging

1.5 ± 0.4

1.2 ± 0.4

p = 0.0007

>1.4

N.S./N.S./67.9

78.9/61.8

Notes: N.S. indicates not stated in the paper; Se: sensitivity; Sp: specificity; PPV: Positive predictive value; NPV: Negative predictive value; Acc: accuracy; Prosp: prospective; Retrosp: retrospective; pCR: pathological complete response; CR: complete response.

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Table 3 Prediction of tumor response on the basis of pre-CRT tumoral ADC.

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It still remains difficult to obtain a precise correlation between DW-MRI findings and the underlying histopathological findings at a microscopic level. Jang et al. tried to correlate histopathological findings of 43 patients with LARC who underwent chemoradiotherapy and for whom pathological complete response was obtained [59]. Of these, restricted diffusion was seen in 18 patients, due to both radiation proctitis and fibrosis, as well as intramural mucin. Mucoid response to chemoradiation, as it appears bright on high b value images, may indeed be mistaken for residual tumor, even when there are no clusters of tumoral cells remaining [59]. In conclusion, although most studies report an increase in tumoral ADC values, as well as a higher percentage change in ADC values after CRT for patients with a favorable response, results are still conflicting and difficult to analyze due to great variation in methodology. Moreover, no threshold ADC value has been found that could be used in clinical practice. Conversely, it is generally admitted that residual viable tumor is more easily recognized on DW-MR images obtained with high b values, standing out on the low signal intensity of the surrounding fibrotic tissue. It is thus recommended to add DW-MRI to MR protocol for rectal tumor reevaluation [21]. 3.4. Lymph nodes evaluation Although the potential of DW-MRI for the assessment of lymph nodes has been demonstrated for head and neck and gynecological tumors, there is not strong evidence for such a utility in rectal cancer nodes [60–63]. One thorough prospective lesion-by-lesion histological validation study has shown that visual evaluation of DWMRI improved the number of detected lymph nodes but that it was not useful for discriminating between benign and metastatic lymph nodes. In this study, calculation of ADC value of lymph nodes allowed discriminating between benign (mean: 1.19 ± 0.27 mm2 /s) and malignant (mean: 1.43 ± 0.38 mm2 /s) lymph nodes with significantly higher ADC values for malignant lymph nodes (p < 0.001) due to the fact that metastatic irradiated lymph nodes undergo necrotic changes. As a limitation; however, in the same study, no threshold ADC value was found to yield sufficient accuracy to allow clinical use [33]. Another recent study confirmed these findings, in terms of improvement of the total nodes detected for primary staging and of absence of significant gain in characterization performance from DW-MRI [49]. 3.5. Rectal cancer: Pelvic recurrence During the surveillance of patients with rectal cancer after surgical treatment, the role of MR imaging has so far been limited to the assessment of tumor resectability in patients with a proven local tumor recurrence [58]. Pelvic MRI may also be used for the detection of local

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recurrence from rectal cancer based on biological or clinical suspicion [27]. Two studies, one retrospective [27] and one prospective [64], have shown that when added to conventional MR imaging, DW-MRI may help identify tumor recurrence within area of fibrosis and better detect all sites of recurrence. They reported sensitivities and specificities of 81–90% (junior reader) and 88–95% (senior reader) for Colosio et al. [64], and of 84–74% (junior reader) and 100–83% (senior reader) for Lambregts et al. [27] for the detection of pelvic recurrence from colorectal cancer, respectively, without DW-MRI, increasing to 98–100% and 95–100% [64] and 89–83% and 100–91% [27], respectively, after addition of DW-MRI (Fig. 8). This added value of DW-MRI appears slight for experienced readers but more obvious for less experienced radiologists. Moreover, DW-MRI, as for detection of tumor response after neoadjuvant treatment, improves interobserver agreement for detection of rectal recurrence [27,64]. Recently, in a series evaluating 30 patients, of which 17 with postoperative recurrence from colorectal cancer, researchers have obtained sensitivities and specificities of 82% and 100%, respectively, in the diagnosis of the recurrence of colorectal cancers after surgery using ADC values obtained from ROIs placed on the ADC maps [65]. Three false negative findings were due to the presence of mucinous adenocarcinomas with high ADC values. Median ADC value in the recurrence group was 1.23 ± 0.41 × 10−3 mm2 /s whereas it was 1.91 ± 0.22 × 10−3 mm2 /s in the fibrosis group, with a significant difference (p < 0.001). When a threshold level of 1.48 × 10−3 mm2 /s was used to determine whether the lesions were recurrence or not, the sensitivity was 82% and the specificity 100%, the predictive positive value 100% and the negative predictive value 81% [65]. In conclusion, we advocate the use of a DW-MRI sequence in addition to standard MR protocol in case of a suspicion of rectal pelvic recurrence. 3.6. Future trends and conclusion Along with the development of minimally invasive treatments or wait-and-see approach, there is a current need for MR evaluation of an irradiated tumor bed with complete response [66]. Morphological MR imaging presentation of rectal tumors during a wait-and-see approach after a clinical complete response in patients with rectal cancer treated with chemoradiotherapy has already been described [67]. DWMRI could be a valuable adjunct in this setting to standard MR imaging for detecting tumor recurrence during the followup of these patients, although so far this issue has not been addressed. FDG PET-CT may be used to assess the metabolic response of the rectal tumor. Although it has been shown that FDG PET-CT can predict the degree of response as early as two weeks after the start of CRT, the assessment of the response is best performed at the end of the interval between CRT and surgery, typically 6 to 8 weeks [68].

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Tumors often demonstrate decreased ADC on DW-MRI and increased standardized uptake values (SUVs) on FDG PET-CT. A significant reduction of SUVs on post-CRT PET of responders compared with non responders has been noted in a number of studies [69,70]. Moreover, Gu et al. [37] recently reported significant negative correlations between ADC and SUV values. Ippolito et al. [71], in a series of 30 patients with LARC who underwent CRT, showed a significantly higher mean value of SUV max in PET/CT before treatment than after treatment along with a significantly lower ADC value before treatment than after treatment. The best predictors cut-off values for response were SUV max of 4.4 and an ADC value of 1.289 × 10−3 mm2 /s with sensitivity, specificity, accuracy, negative predictive value, and positive predictive values of 77.3%, 88.9%, 80.7%, 61.5%, and 94.4%, respectively. It is of note that to date, there is not any clear knowledge regarding superiority of any of these two imaging modalities for evaluation of rectal tumor response after treatment and that PET/CT needs to be formally compared with MRI. Measuring ADCs requires a considerable time investment for a radiologist in a busy clinical practice. Furthermore, when considering the use of ADC for response assessment, one should bear in mind that ADC values show large variations caused by differences in MR equipment and DW-MRI parameters and methods of analysis. Although normalized ADC values have been suggested, mainly for pancreas ADC evaluation, no studies have ever been performed to investigate this issue in the rectal field [72]. Further research should therefore focus on imaging standardization and analysis protocols in order to obtain reproducible threshold ADC values.

Conflict of interest statement There is no conflict of interest.

Reviewers

Fig. 8. Axial high b value MR diffusion-weighted image optimally depicts a pelvic recurrence of a colorectal adenocarcinoma in a 60 year-old patient who was operated on 4 years ago (white arrow (b)). The recurrence is seen as a high signal intensity irregular nodule that is less conspicuous on T2weighted MR axial images (black arrow (a)). On ADC map (c), recurrence is seen displaying relatively low signal (white arrow).

Boris Guiu: MD, CHU de Dijon, Service de Radiodiagnostic et d’Imagerie médicale diagnostique et thérapeutique 2, boulevard du Maréchal de Lattre de Tassigny, F-21079 Dijon Cedex, France. Stephanie Nougaret: Department of Imaging, Hôpital Saint-Eloi, CHU Montpellier, F-34295 Montpellier Cedex 5, France. Sabine Schmidt: MD, CHUV University Hospital Canton of Vaud, Department of Medical Radiology, 46 rue du Bugnon, CH-1011 Lausanne, Switzerland. Pierre E Bize: MD, University Hospital of Lausanne, Diagnostic and Interventional Radiology, 46 rue de Bugnon, CH-1011 Lausanne, Switzerland. Jean-Claude Horiot: MD, PhD, Radiation Oncologist, Clinique de Genolier, 5 route du Muids, CH-1272 Genolier, Switzerland.

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Biographies

17

of 280 papers, mainly focused on abdominal imaging and the editor of two books. Paul Fornes M.D., Ph.D., 53-year-old, is professor of pathology and forensic medicine at the university hospital of Reims, France. He has published or co-published over 50 papers. Pascal Rousset M.D., 36-year-old, took his medical degree in Paris in 2003. He is associate professor of radiology at the university hospital of Lyon, France. He has published or co-published 26 papers, mainly focused on pelvic imaging and Magnetic resonance imaging.

Truong Luong Francis Nguyen 30-year-old, M.D. He took his medical degree in 2013 in Reims university hospital and is a fellow in the radiology department specialized in abdominal and oncology imaging.

Reza Kianmanesh M.D., Ph.D., is Head of the Department of abdominal surgery at the university hospital of Reims, France. He has published or co-published over 40 papers.

Philippe Soyer M.D., Ph.D., 54-year-old, is Head of Imaging and Nuclear Medicine at Group Hospitalier Saint-Louis-Lariboisière in Paris, France, Chairman of the Department of Abdominal Imaging, at the Lariboisière University Hospital and full professor of abdominal imaging at the Diderot-Paris 7 University. He is the author or co-author

Christine Hoeffel M.D., Ph.D., 46-year-old took her medical degree in Paris in 1992. She is professor of radiology at the university hospital of Reims, France. She has published or co-published over 130 papers, mainly focused on abdominal imaging and Magnetic resonance imaging.

Please cite this article in press as: Nguyen TLF, et al. Diffusion-weighted MR imaging of the rectum: Clinical applications. Crit Rev Oncol/Hematol (2014), http://dx.doi.org/10.1016/j.critrevonc.2014.07.002