Diffusione e spettroscopia

Transcription

1 Institute for Cancer Research and Treatment Candiolo -Torino (Italy) Unit of Diagnostic Imaging - Director Dr. Daniele Regge Diffusione e spettroscopia Laura Martincich Parma Aprile 2011

2 What is Molecular Diffusion? How can we detect Molecular Diffusion on MRI? Which information provides DWI? How can we apply DWI on the breast?

3 What is Molecular Diffusion? Anisotropic Diffusion Biological tissues are highly heterogeneous media that consist of o various compartments and barriers with different diffusivity The movement of water molecules during diffusion random displacement is impeded by compartmental boundaries and other molecular barriers, that the diffusion distance is reduced compared to unrestricted diffusion Hagmann, Radiographics 2006 O Flynn, Breast Cancer Research 2011

4 How can we detect Molecular Diffusion on MRI? b value =0 and b value >0 Short acquisition time QuickTime and a Cinepak decompressor are needed to see this picture. Courtesy of Dr. Bracco, Medical Physics IRCC

5 Which information provides DWI? High diffusion = Major loss of signal e.g. liquid content Low diffusion = Minor loss of signal e.g. high cellular density tissues

6 Qualitative information: ADC maps + = b 0 s/mm 2 b 900s/mm 2

7 Quantitative information: ADC value ADC= -(1/b)In(S/S 0 ) S and S 0 = Signal intensity with and without diffusion sensitisation b = level of sensitisation to diffusion of the sequence Related to cellular density and extracellular volume Lee, Clin Cancer Res 2007 ADC ± = 0.96±0.3x10 0.3x10-3 mm 2 /s

8 How can we apply DWI on the breast? Characterisation of Breast Lesion Improving specificity and PPV of DCE-MRI Monitoring the tumoural response to medical treatment

9 Characterisation of Breast Lesions Studies included if: 1.5T Diagnostic criteria clearly stated Calculation of ADC and SD Tsushima, JMRI 2009

10 Characterisation of Breast Lesions ADC Malignant mm 2 /s ADC Benign mm 2 /s ADC Normal mm 2 /s Tsushima, JMRI 2009

11 Characterisation of Breast Lesions Lesion Presentation Partridge, AJR 2009

12 Characterisation of Breast Lesions Lesion Size Partridge, AJR 2009

13 Characterisation of Breast Lesions Woodhams, AJR 2009

14 CARCINOMA INFILTRANTE DELLA MAMMELLA. Istotipo: mucinoso pt2 pn0(i-)(sn) G2 ER 98%, PgR 99%, HER2 0+, Ki-67 21%

15 CARCINOMA DUTTALE INFILTRANTE ER-,, PgR-,, HER 3+

16 How can we apply DWI on the breast? Characterisation of Breast Lesion Improving the specificity and PPV of DCE-MRI Monitoring the tumoural response to medical treatment

17 Improving specificity and PPV of DCE-MRI

18 Improving specificity and PPV of DCE-MRI 83 lesions recommended for biopsy (BIRADS 4,5) PPV DCE-MRI alone 37% lesions <1cm 35% PPV DWI + DCE-MRI 47% lesions <1 1 cm 52% prevention of benign biopsy 17% Partridge, AJR 2009

19 How can we apply DWI on the breast? Characterisation of Breast Lesion Improving specificity and PPV of DCE-MRI Monitoring the tumoural response to medical treatment

20 Monitoring the tumoural response to medical treatment Background based on Preclinical models Higher ADC values were observed in treated cancers with respect to untreated DWI has the potential: to detect and quantify cellular changes that occur in response to therapeutic intervention prior to macroscopic changes in size to provide a window to peer into the temporal dynamics of drugs action to be an imaging surrogate for predicting the tumoral response Author Cell line Therapy Timing from baseline DWI ADC increase in treated cancer ADC in control group p Galons 1999 MCF7/S Taxane 2 days 50% Resistant Cells MCF7/D40 0% na Lee 2007 MX-1 Human BC Cyclophosphamide 4-77 days 94% Untreated cancer 17% Galons, Neoplasia 1999 Ross, Mol Cancer Therapy 2003 Theilmann, Neoplasia 2004 Lee, Clin Cancer Res 2007

21 ADC value as biomarkers in the tumour response Water motion within a tumour increases over time after medical treatment, t as a result of membrane damage with subsequent reduction of cells s density (apoptotic cell death) Thoeny HC, JMRI 2010

22 Monitoring tumour response to neoadjuvant medical treatment 70 locally advanced breast cancer in 69 patients Imaging: before and after PCT Standard of Reference: histhopatology (pcr vs size of residual disease) d Sensitivity 97% Specificity 89% Accuracy 96% Sensitivity 93% Specificity 56% Accuracy 89% Woodhams, Radiology 2010

23 CDI ER 90%; PgR 80%; Herceptest 3+, Ki 67 48% p r e p o s t

24 p r e p o s t PARENCHIMA MAMMARIO CON AREA DI FIBROPLASIA CICATRIZIALE, VEROSIMILE ESITO DI PRECEDENTE TRATTAMENTO CHEMIOTERAPICO Grado di risposta istopatologica a pregressa CT neoadiuvante: 5/5 (risposta completa) sec. Smith et al [JCO 2002 ].

25 Monitoring the tumoural response to medical treatment Clinical applications PCT: 3 cycles of Epirubicin and Ciclophosphamide Imaging: at Baseline and after 1 st and 2 nd cycles p=0.05 p=0.04 n.s. n.s.

26 Pre PCT During PCT Histopathological grade of response: 5/5 No invasive tumour cells identifiable in the sections from the site of the previous tumour Core-biopsy: IDC

27 Pre PCT During PCT Histopathological grade of response: 1/5 Some alteration to individual malignant cells but no reduction in overall numbers as compared with the pretreatment core-biopsy Core-biopsy: ILC

28 Diffusion Weighted Imaging Cancer gene pathways Yenkeelov, Magn Reson Imaging 2007 Vogelstein, Nature Med 2004

29 Potential tool in Monitoring the tumoral response to targheted-therapies therapies The objectives were to access molecular changes with bevacizumab alone and in combination with chemotherapy. Those included tissue VEGF, activated VEGFR2 status (phosphorylated VEGFR2 [p- VEGFR2]), total VEGFR2, tumor MVD, tumor cell apoptosis, and proliferation. The increase of apoptosis again persisted with addition of chemotherapy (72.7%; P=.013)

30 A c q u i s i t i o n P o s t P r o c e s s i n g? Which and how many b-value? b? Standardization and Reproducibility? ADC value thresholds? Pitfalls and False cases

31 Which and how many b-value? b Diffusion weighting is expressed by the b-value b (s/mm 2 ) The loss of signal due solely to diffusion is described by the equatione quation: S = S 0 e -badc S and S 0 = signal intensity with and without diffusion sensitisation ADC = Apparent Diffusion Coefficient b = level of sensitisation to diffusion of the sequence b depends on: Time interval between the two pulse gradients Intensity of the two pulse gradients Duration of the two pulse gradients As b increases, so too does the weighting diffusion of the sequence

32 Which and how many b-value? b Perfusion-insensitive insensitive ADC values calculation should include low b value to extinguish flow signal For ADC quantification two b values should be used ( 100sec/mm( 2 and 500 but 1000sec/mm 2 ) with a monexponential decay. Padhani, Neoplasia 2009

33 Which and how many b-value? b b 0, 250, 500, 750 and 1000 s/mm 2 (scanner GEHC) ADC calculation using 5 b-values (0 and >0) These findings suggest that the higher b values are useful to distinguish benign from malignant lesions and that there is no need to use multiple b values in the DWI sequence, saving examination time Arantes Pereira, AJR 2009

34 Which and how many b-value? b Large maximum b value b 0 s/mm 2 Advantages elimination of signals from normal (noncancerous) tissue, better detectability of malignant lesions Disadvantages Decreased SNR b 900s/mm 2 Arantes Pereira, AJR 2009 Tsushima, JMRI 2009

35 Which and how many b-value? b 500s/mm s/mm 2 Multicentric LIC. pt3(m) pn3a

36 Drawing the ROI Avoiding necrosis? Within the lesion margins Ideally, the region of interest (ROI) is contoured around lesions using images with the highest contrast between lesion and normal tissue. Subjective placement of smaller ROIs within lesions is not recommended particularly for response assessment studies Padhani AR, Neoplasia 2009 Liquefactive necrosis is characteristic of bacterial or fungal infections, because microbes stimulate the accumulation of inflammatory cells. Whatever the pathogenesis, liquefaction completely digests the dead cells.. The end result is transformation of the tissue into a liquid viscous mass. Coagulative necrosis implies preservation of the basic outline of the coagulated cell. The affected tissues exhibit a firm texture. Presumably, the injury or the subsequent increasing intracellular acidosis denatures not only structural proteins but also enzymes and so blocks the proteolysis of the cell. The process of coagulative necrosis, with preservation of the general tissue architecture, is characteristic of hypoxic death of cells in all tissues Robbins, Elsevier 2007

37 Drawing the ROI CDI G3 ER- PgR- HER2 3+

38 ADC value cut off? Sasaki, Radiology 2008

39 ADC value cut off? ADC Malignant mm 2 /s ADC Benign mm 2 /s ADC Normal mm 2 /s Tsushima, JMRI 2009

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41 Pitfalls and false cases

42 Pitfalls and false cases 2008 BCS for right DCI 2011 Left nodal MTS

43 Pitfalls and false cases

44 Pitfalls and false cases Microfocolai multipli di DCIS. Istotipo: piatto e cribriforme; Grado nucleare: alto; Necrosi comedonica: presente

45 Pitfalls and false cases Microfocolai multipli di DCIS. Istotipo: piatto e cribriforme; Grado nucleare: alto; Necrosi comedonica: presente

46 Characterisation of Breast Lesions 13 subjects with breast cancer 16 Malignant lesions Intraindividual study Small lesions were visible more clearly at 3.0 T

47 Conclusion DWI is a promising but still investigational MR technique Limitation DCE-MRI guidance for (small) lesion detection Advantages for the application in clinical practice Short acquisition and post processing time Quantitative approach No contrast media administration required

48 Conclusion It could be a way To improve the diagnostic performance of breast MRI in the characterization of small MRI enhancing areas To detect tumoural changes due PCT Monitoring response to PCT in association with DCE- MRI before and after PCT and as a single technique during PCT Effectiveness of target-therapy therapy High quality equipment/technical consinstency

49 Spectroscopy

50 H 1 Magnetic Resonance Spectroscopy (MRS) Imaging of molecules, which generates detectable peaks at MRS MRS does not generate an image of the tumour directly, but the spectroscopic data can be obtained from a well localised area (voxel) Provides biochemical information about biological tissues by a generation of images of metabolites distribution (spectrum)

51 H 1 Magnetic Resonance Spectroscopy (MRS) ν Space Chemical structure (metabolites distribution) Magnetic Resonance Imaging Magnetic Resonance Spectroscopy

52 H 1 Magnetic Resonance Spectroscopy (MRS) Metabolites Spectral Decomposition Water 4.7 ppm ( ) Lipid 1.3 ppm (0-2.5)

53 H 1 Magnetic Resonance Spectroscopy (MRS) Metabolites Choline compounds peak at 3.2ppm is considered a marker of active tumour Spectral Decomposition I D C Choline Compounds 3.2 ppm ( ) 3.34) Choline, phosphocoline, glyceroposphocholine, myoinositol, taurine Stanwell, Eur Radiol 2005 Sardanelli, Eur Radiol 2006

54 H 1 Magnetic Resonance Spectroscopy (MRS) Metabolites Imbalance between biosynthesis and catabolism of phospatidyl-choline Podo, NMR Biomed 1999

55 H 1 Magnetic Resonance Spectroscopy (MRS) Technique (1,5T) Single Voxel Spectroscopy The acquisition of a spectrum related to a single volume of interest (VOI) including the lesion detected Voxel shimming PRESS sequence Point Resolved Spectroscopy STEAM sequence Stimulated Echo Acquisition Mode Lesion size influences MRS

56 H 1 Magnetic Resonance Spectroscopy (MRS) Technique Lipid Sidebands from spurious echoes from mobile lipids Water Reduced spectra quality Obscuration of choline peak Sardanelli, Eur Radiol 2006 Bartella, Radiographics 2007

57 H 1 Magnetic Resonance Spectroscopy (MRS) Technique IDC Fibroadenoma Sidebands from spurious echoes from mobile lipids

58 H 1 Magnetic Resonance Spectroscopy (MRS) Technique Single Voxel Spectroscopy Water Unsuppressed and suppressed data

59 H 1 Magnetic Resonance Spectroscopy (MRS) Technique Single Voxel Spectroscopy PRESS sequence STEAM sequence Set up (5-10min) Water suppression Voxel shimming Check of field homogeneity and efficacy of prepulses + Inclusion of prepulses for water and fat suppression Echo time 135ms TR 1,5-3sec Signals acquired Acquisition Time 3-12min Bartella, Radiographics 2007

60 H 1 Magnetic Resonance Spectroscopy (MRS) Post Processing Reference Data r[n] Phase Correction DC Mixing Zero Phasing Linear Phase Correction Phase Spline Smoothing Phase Correction Vector c[n] Water Subtraction Water-suppressed Data s[n] Phase Correction Non quantitative/semiquantitative information Detection vs Non Detection of Choline peak Choline Signal (SNR) FFT S[k] Sardanelli, Eur Radiol 2006 Bartella, Radiographics 2007

61 H 1 Magnetic Resonance Spectroscopy (MRS) Clinical Application at 1,5T Characterization of Breast Lesions Potential obviation of biopsy in 57% of the cases Bartella, Radiographics 2007

62 H 1 Magnetic Resonance Spectroscopy (MRS) Clinical Application at 1,5T

63 Conclusion MRS may help in improving the diagnostic value of Breast MRI Evaluation of one lesion at a time MRS Established technique Approval by USA FDA Limitations Selection of the cases Lesion size: voxel >1cm 3 Presence of hematoma or metallic clip Long acquisition time Non quantitative method Dedicated team

64 DWI vs MRS H1 MRS was useful for characterizing breast lesions measuring 15mm or larger, and Diffusion-weighted imaging was useful for characterizing lesions of any size

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