PHYSICS OF DWI AND ITS CLINICAL APPLICATION.pptx

MRI physics

1. PHYSICS OF DWI AND ITS CLINICAL APPLICATION BY DR.NAHID NIAJ(PGT) MODERATOR:DR.ASIM DE(PROFF AND HOD)

2. Learning outcomes 1.What is Diffusion ? 2.How DWI is acquired? 3.Artefacts and pitfalls. 4.Clinical applications. 5.Advance techniques.

3. INTRODUCTION

4. It was originally described by Le Bihan 30 years back. The basic principle of DWI is based on the Brownian motion of water molecules which takes place in the body and it utilizes motion sensitizing gradients to study this motion. It provides unique information at microstructural and functional level which can be used to characterize cellular dense lesions and this has applications in oncology. Diffusion can be assessed both qualitatively and quantitatively. It is quantified by the parameter Apparent Diffusion Coefficient (ADC) which is derived from the diffusion images and is a scalar quantity .

5. BASIC PRINCIPLE Water molecules in the body undergo a random motion called “Brownian motion” which is as a result of body heat. The intracellular diffusion is more hindered than the extracellular component because of the presence of cell membrane and intracellular components. In case of malignant tumors the cells are densely packed with large nuclei and scanty cytoplasm which results in restriction of diffusion. On the other hand, benign cells are loosely packed with small nucleus and abundant cytoplasm that facilitates diffusion. The measured diffusion is termed as ADC which is expressed in mm2 /s.

6. There are various types of sequences with diffusion sensitizing gradients incorporated within but the basis of all of them is the technique suggested by Stejskal and Tanner in 1965 and implemented by Le Bihan in 1986. Their technique essentially involves adding two diffusion sensitizing gradient, one on either side of 180° refocusing pulse. These gradient lobes have the same magnitude but are opposite in direction called dephasing and rephasing gradient . The 180° pulse will eliminate the dephasing due to the inhomogeneity of external magnetic field.

7. The water molecules whose diffusion is not restricted will get dephased by the first gradient lobe and during the process the molecules will move to another location in which the water molecules will be subjected to a different magnetic environment so that the rephasing pulse will not exactly rephase them to their original state. This will cause attenuation of signal from these water molecules as they are not exactly rephased to produce a strong echo. Whereas, water molecules whose diffusion is restricted will not move and they will be subjected to the same magnetic environment and the dephasing and rephasing gradients will exactly neutralize each other and their spins will be in phase to produce a strong echo.

8. These diffusion gradients can be applied in any of the axis (x, y, z) or in any combination and it is called diffusion sensitizing direction. This diffusion gradient addition can be applied in spin echo or in steady state sequences as long as they have a long TE to accommodate them and this is the reason why the diffusion sequences are T2 weighted

9. DWI SEQUENCES AND OPTIMIZATIONS

10. ECHO PLANAR IMAGING: After the initial excitation pulse, diffusion gradient pair, a series of fast gradient oscillations is applied for read-out and the entire k-space is filled with a long echo train. This can be implemented as spin echo EPI or gradient echo EPI. Typically, separate acquisition is done for 3 orthogonal axes which are averaged into one final image. One of the disadvantages of EPI is significant phase shift gets accumulated between the water and fat protons and this leads to geometric distortion along the phase encoding direction.

11. So, it is of paramount importance that all EPI sequences are done with fat suppression. There are various methods of fat suppression such as water only excitation, chemical fat suppression, short-tau inversion recovery (STIR) and spectral selection attenuated inversion recovery (SPAIR)

12. Schematic representation of DW spin echo EPI sequence showing the motion probing gradients (arrows) used to detect the diffusion of water molecules and multiple gradient oscillations (outlined arrow) to generate echoes. In this single shot sequence, the entire k space is filled in single excitation .

13. HALF FOURIER SINGLE SHOT TURBO SPIN ECHO(HASTE) This is an alternative to DW-EPI sequence and it is also relatively insensitive to motion and can perform a single shot read-out and the entire k-space is filled in single excitation. An important difference from EPI is that 180° refocusing pulse is applied during each read-out so that the phase shift accumulation because of long echo train is avoided .

14. FIG: Schematic representation of single shot fast spin echo sequence showing motion probing gradients (arrow) to detect the water diffusion. Multiple 180° refocusing pulses (outlined arrow) rather than gradient oscillations are used to generate echoes.

15. B VALUE The magnitude, duration of diffusion gradient applied and the duration between the dephasing and rephasing lobe determines the sensitivity of the sequence to water diffusion which is described by a factor called diffusion weighting factor or b factor (s/mm2 ). Usually, the magnitude is kept maximal and the other two are altered to get a desired b value. At least 2 b values are needed for the calculation of ADC and multiple b values are used for more accurate quantification. When multiple b values are used the TE time which is maximum for highest b value is usually kept constant for all b values for better quantification.

16. The usual thumb rule is that b value is about inverse of the expected ADC value. The SNR of the sequence is grossly affected by the b value selection. At the same time low b value will not generate an image whose contrast characteristics are truly based on diffusivity of water molecules. So optimal b value is a balance between the SNR required for quantification and the diffusion contrast of the image. High b values (>1000) are used in imaging techniques like diffusion weighted whole body imaging with background body signal suppression (DWIBS) in which background signal suppression is important.

17. ADC AND EXPONENTIAL IMAGE ADC image is a parametric map which is derived from the DW image and it is devoid of T2 shine through. It needs images acquired at minimum of two b values to calculate ADC and in present day scanners the calculation of ADC map is automatic. Since ADC map is the grayscale representation of pixel by pixel ADC values calculated from diffusion images, the artifacts associated with the diffusion sequences will also get reflected.

18. Another way to remove the T2 effect on the diffusion weighted image is generating an exponential image which is done by calculating the ratio of diffusion weighted image and b0 image. Contrary to ADC map, hyperintensity on the exponential image corresponds to hypointensity on ADC map and suggests diffusion restriction and vice versa.

19. FIG: Graph illustrates the logarithm of relative signal intensity (SI) (y-axis) versus b value (in this case, 0 and 500 sec/mm2 ) (x-axis) for tumor and normal tissue. The slope of the “tumor line” is less than that of the line representing normal tissue, which translates into lower signal on the ADC map .

20. AFRTEFACTS AND PITFALLS OF DWI

21. T2 Shine through: The SE sequence used in diffusion-weighted imaging is T2 weighted, Therefore, in tissues with very long T2 relaxation times, the strong T2 signal may be mistaken for restricted diffusion, a phenomenon known as T2 shine-through effect. The easiest way to distinguish between restricted diffusion and T2 shine-through is to generate an ADC map, on which the former appears as an area of low signal intensity (low ADC values) and the latter as a high-signal-intensity area

22. There are other techniques for reducing T2 shine through, such as using (a) a high b value and a short echo time to decrease the T2 signal, or (b) an exponential imaging technique in which a new image is generated by using the ratio of the diffusion-weighted image divided by the non-weighted image (b = 0).

23. Susceptibility Artifact An echoplanar sequence is used for diffusion weighted image acquisition and is especially susceptible to magnetic field heterogeneities , e.g in abdominal imaging is particularly challenging due to the presence of air within the gastrointestinal tract and lung bases . Other sources of susceptibility artifact include medical devices ( eg , metallic stents, surgical clips) and grafts. One way to reduce susceptibility artifact is to shorten the echo time and increase the bandwidth.

24. Motion Artifact Motion artifact due to multiple constantly moving organs is a major source of image degradation in whole-body diffusion-weighted imaging. Motion artifact is more pronounced along the phase encoding direction, where it creates “ghost” images. Increasing the speed of image acquisition, which is now possible with single-shot echoplanar imaging, and using parallel imaging are possible ways to decrease this artifact.

25. Effect of Contrast Material This effect appears to be most pronounced in the renal parenchyma due to a high concentration of contrast material excreted into the collecting system. The ADC signal of the renal parenchyma is significantly lower on postcontrast diffusion-weighted images (obtained an average of 11 minutes after contrast material injection) than on pre-contrast images.

26. FIG: Schematic representation of signal intensities on T2W, DW sequence and ADC map for disease entities and artifacts which are commonly encountered in day-to-day practice.

27. Applications of DWI

28. BRAIN EVALUATION DWI has become a gold standard in imaging of stroke to identify the infarct core mainly because of its ability to detect the infarcted area within minutes after the onset of symptoms, much earlier than other MRI sequences. DWI is highly sensitive (81–100%) and specific (86–100%) in detecting the ischemic area within 12 hours of symptom onset. DWI-Perfusion mismatch helps in identifying the ischemic penumbra and subsequently I.V thrombolysis. The diffusion imaging in brain is further enhanced by newer sophisticated techniques such as diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI).

29. It helps in characterization of tumors and their response assessment to treatment. Solid gliomas which show low ADC values are associated with higher grade. The DTI also has a proven role in the preoperative assessment of brain tumors. Changes in ADC values in the first few weeks after the therapy are found to be noninvasive biomarkers for response to therapy and it can be used for prognostication also.

30. Breast Evaluation Multiple combinations of b values have been proposed for the accurate differentiation of benign and malignant lesions. ADC values calculated using b values of 0 and 750 sec/mm2 were slightly more useful than those calculated using other combinations. The other study suggested that the use of b values of 50 and 850 sec/mm2 resulted in the highest accuracy (95%) . The mean ADC value of benign lesions is significantly higher than that of malignant lesions.

31. FIG:Poorly differentiated invasive ductal breast carcinoma in a 44-year-old woman. (a) Sagittal diffusion-weighted image (b = 800 sec/mm2 ) shows two nodules with restricted diffusion (arrowheads). (b) Sagittal ADC map shows restricted diffusion throughout the upper (solid) tumor and in the peripheral rim of the lower (necrotic) mass, with higher ADC values in the center of the mass. (c) Dynamic contrast-enhanced MR image with superimposed color coding shows increased permeability in the region of the cancer

32. Diffusion-weighted imaging of the breast has shown promise for the evaluation of tumor response to neoadjuvant chemotherapy. Various reports have shown ADC value to be more useful in assessing tumor response after the first cycle of neoadjuvant chemotherapy and late tumor response after the third cycle than morphologic parameters such as tumor volume and dynamic contrast-enhanced MR imaging parameters . In a 2009 study of patients with locally advanced breast cancer, Sharma et al reported a mean percentage increase in ADC value of 51% ± 31.5 in responders, compared with 14.3% ± 13.1 in non-responders.

33. Hepatic Evaluation Tumor Detection DWI is being applied for the detection of liver metastases. L ow b-value images (e.g., b = 50–150 s/mm 2 ) that suppress the high-signal flow from the hepatic vessels, resulting in black blood images, have been found to be useful for lesion detection. Tumor Characterization To characterize lesions in the liver using DWI, b values ranging between 0 and 500 s/mm 2  are appropriate.

34.   It is often difficult to distinguish different types of solid lesions from one another in the liver by visual assessment alone. For example, a hemangioma will exhibit restricted diffusion and can mimic the appearance of a metastasis at DWI . Using quantitative evaluation, investigators have found that benign liver lesions, such as cysts and hemangiomas , have higher mean ADC values (e.g., 2.45 × 10 –3  mm 2 /s) than malignant lesions, such as metastases and hepatocellular carcinoma (e.g., 1.08 × 10 –3  mm 2 /s) The ADC has also been used to distinguish abscesses, which have low ADC values, from cystic and necrotic metastases, which have higher ADC values.

35. High-b-value diffusion-weighted imaging in combination with contrast-enhanced MR imaging and ADC mapping can be used to further assess the lesion morphologically. Highly cellular benign lesions such as focal nodular hyperplasia and adenoma are the most problematic because they have intermediate ADC values close to those of malignant lesions, including hepatocellular carcinoma. Segmented EPI,HASTE,SSFP and PROPELLER-these are some technique to overcome the motion artefacts.

36. FIG: Differentiation between malignant and benign hepatic lesions. (a–c) Hemangioma in a 58-year-old woman,(d–f) Hepatocellular carcinoma in a 62-year-old woman.

37. FIG: Response to therapy administered to a 19-year-old man who presented with leiomyosarcoma of the left hepatic lobe

38. KIDNEY EVALUATION The pattern of increased signal intensity at diffusion-weighted imaging and decreased ADC values at ADC mapping in RCC is similar to that in solid malignant lesions of other organs. Significantly lower ADCs seen in solid RCCs than in simple or mildly complex cysts and oncocytomas, Another study demonstrated higher ADC values in RCC than in transitional cell carcinoma (2.71 × 10-3 mm2 /sec versus 1.61 × 10-3 mm2 /sec). Amongst clear cell, papillary, and chromophobic RCCs ,clear cell RCC shows the largest mean ADC (1.698 × 10-3 mm2 /sec) value.

39. Male Pelvis There is increasing evidence that diffusion weighted imaging improves sensitivity and specificity in the detection of prostate cancer. Recent studies have also shown diffusion-weighted imaging to have a positive impact on tumor staging and the assessment of tumor aggressiveness and treatment response. The usefulness of diffusion-weighted imaging as a biomarker for local recurrence of prostate cancer and in the evaluation of metastatic disease has also been demonstrated.

40. For prostate MR imaging, b values of 0 and 800–1500 sec/mm2 have typically been used, depending on scanning parameters. For prostate cancer staging, diffusion weighted imaging may be helpful in the assessment of seminal vesicle involvement by demonstrating low ADC values in that region (provided no hemorrhage is present on T1-weighted images), as well as in the staging of lymph nodes, since malignant nodes tend to have lower ADC values .

41. Female Pelvis The addition of diffusion weighted imaging to the conventional MR imaging protocol allows the assessment of oncologic entities in the female pelvis, from lesion detection and characterization to staging of malignancies. Endometrial and cervical cancer have low ADC values compared to normal endometrium and cervical stroma. DWI is also helpful in seeing invasion where contrast study is contraindicated.

42. Monitoring Treatment Response Effective anticancer treatment results in tumor lysis, loss of cell membrane integrity, increased extracellular space, and, therefore, an increase in water diffusion. The results of animal studies have confirmed that after the initiation of chemotherapy, radiation therapy, or novel therapy, an increase in the ADC value may be observed in those responding to treatment.

43. Predicting Treatment Response Studies in rectal carcinoma, cerebral gliomas ,and colorectal hepatic metastases ,have shown that cellular tumor with low baseline pre-treatment ADC values respond better to chemotherapy or radiation treatment than tumors that exhibit high pre-treatment ADC values. One possible explanation is that tumors with high pretreatment ADC values are likely to be more necrotic than those with low values. Necrotic tumors frequently are hypoxic, acidotic, and poorly perfused, leading to diminished sensitivity to chemotherapy and to radiation therapy.

44. Whole-Body Diffusion-weighted Imaging It is clear that by combining anatomic imaging ( eg , T1- and T2-weighted imaging) with whole-body diffusion-weighted imaging, early changes within the primary tumor and metastatic sites can be visualized, which can provide important information about treatment response and permit the development of individualized treatment regimens. The DWIBS is a whole body diffusion technique which is done typically using DW-EPI sequence and STIR for fat suppression.

45. Typically, b value in the range of 1000 is used which will provide good background suppression. But, more than one b value can be used if quantification is needed at the expense of time. These multiple slices are fused and usually displayed in inverted grayscale with white background similar to PET images. This technique makes use of a free breathing approach during imaging.

46. FIG: Metastatic adenopathy in a 71-year-old man with a history of prostate cancer who presented with a rising prostate-specific antigen level. (a) Whole-body T2-weighted MR image shows an area of slightly increased signal intensity (arrowhead) in the left side of the pelvis. (b) Whole-body ADC map shows restricted diffusion within the lesion (arrowhead), a finding that is compatible with metastatic left iliac adenopathy . (c) Carbon-11 positron emission tomographic image shows the lesion (arrowhead) with increased radiotracer activity and an increased standardized uptake value of 5.6.

47. FIG:T2-weighted and segment of whole-body diffusion-weighted images. T2-weighted image ( A ) and diffusion-weighted inverted gray-scale maximum-intensity-projection (b = 1,000 s/mm 2 ) image ( B ) of pelvis show nodal disease along both pelvic sidewalls in 63-year-old man with colon cancer. By performing imaging at multiple stations, whole-body diffusion map can be constructed.

48. ADVANCED DWI TECHNIQUES Diffusion Tensor Imaging Diffusion tensor imaging (DTI) has both magnitude and the directional information of diffusion. The DTI is extensively studied in brain where it is used to show the white matter tracts. It uses the property of anisotropy of diffusion of water molecules. Because of the myelinated axons in the brain white matter, the diffusion is unhindered along the direction of the fiber which is called diffusion anisotropy.

49. To obtain the directional component gradient lobes are used in multiple directions and the resulting data is processed. As a result each voxel has the effective direction of diffusion which is called as Eigen vector and the value of diffusion in that direction is called as Eigen value. This information is used to reconstruct fiber tract network in the brain which is called as tractography. Fractional anisotropy (FA) reflects how dominant one particular water movement direction in a voxel is. It varies from 0 to 1 and can be considered a biomarker of axonal integrity (usually decreased in white matter pathologies).

50. Intravoxel Incoherent Motion The IVIM is based on the fact that the diffusion imaging at low b values (b 0-100) will have the effect of both the tissue perfusion (pseudo-diffusion) and the true diffusion. They described D* as pseudo-diffusion coefficient which is dependent on capillary perfusion. This effect gets reduced at high b values where the true diffusion predominates. This is one proposed reason for decrease in ADC values with increase in b value

51. The current model available in most of the commercial scanners for the calculation of ADC is based on monoexponential function, considering that the logarithm of relative signal intensity plotted against the b value is a straight line which is not true. The IVIM model suggests that the relationship between the signal intensity and b value is not monoexponential (Gaussian) rather biexponential (non-Gaussian). It has been shown to differentiate low grade brain tumors from high grade tumors and shown to differentiate benign focal lesions from malignant lesions in liver.

52. Diffusion Kurtosis Imaging Diffusion of water molecules in a homogeneous solution follows a Gaussian distribution whereas diffusion of water molecules in biological tissues actually follows a non- Gaussian distribution. This difference in distribution is because of cellular microstructure (cell membranes and organelles) which alter the water diffusion. The modern MRI scanners can generate DW images with b values more than 2000. Diffusion signals at high b values are predominated by non-Gaussian distribution which can be depicted using a sophisticated model known as diffusion kurtosis imaging (DKI).

53. DKI can reflect the intracellular changes such as nuclear cytoplasmic ratio and intracellular heterogeneity. They provide information which can be clinically relevant in oncological imaging.

54. Computed DWI High b value diffusion weighted images have higher contrast resolution and lesser T2 shine through effect which can be helpful in lesion detection. However, acquiring high b value images requires a capable scanner with high field strength and longer acquisition time. It will also lead to loss of SNR and can introduce motion artifacts. To overcome these challenges, one can compute any b value DW image with the help of the acquired low b value images and the ADC values. The principle of computed DWI is based on the mono, bi or tri-exponential model where in the assumption is that all the data points of acquired b value images fall in a straight line on the signal intensity curve.

55. CONCLUSION DWI is an evolving technique that provides a new paradigm for tissue characterization. Its provides both qualitative and quantitative insight in to complex diffusion mechanisms. It has an important role in tumor characterization in oncology. DW sequences must be interpreted in conjunction with other MR sequences to avoid the pitfalls of this technique.

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