6. VIABILIDAD ECONÓMICA
6.2. Análisis de las ventajas y desventajas competitivas
MR spectroscopic imaging of the prostate provides 3D spatially localized information about the presence of specific metabolites in a selected part of the proton spectrum in prostate tissue, such as citrate (2.60 ppm), choline (3.20 ppm), creatine (3.04 ppm) and polyamines (multiplet around 3.10 ppm) (Fig. 2.3). A high level of citrate is an important marker for healthy or benign prostate tissue, whereas prostate cancer is characterized by a combination of a reduced amount of citrate and increased choline levels (41,42). The ratio of signal integrals of choline + creatine to citrate combines these effects and is used as a marker for prostate cancer. This quantitative marker can be analyzed separately or in combination with the choline-to-creatine ratio in the standardized threshold approach (43,44), providing a reproducible measure (45) to be used to predict tumor presence and absence in both the peripheral as well as the transition zone, and it can help in determining prostate cancer aggressiveness (46–49).
Since the signal in MR spectroscopy results from low abundant metabolites instead of from highly abundant water, an increase in intrinsic SNR by moving to a higher field strength is directly advantageous for this technique. Long acquisition times are required at 1.5 T to obtain 3D datasets with voxel volumes of about 0.5 cm3,
which corresponds to the size of clinicallysignificant tumors (50,51). At 3 T, 1H MRSI
can be performed at a resolution of 0.6 cm3 effective voxel volume (nominal voxel
resolution 6 x 6 x 6 mm) within 9 min (52) using an endorectal coil, or even without an endorectal coil in the same time at 1.0 cm3 effective voxel volume (nominal voxel
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Figure 2.3 - Typical spectra of voxels in the healthy peripheral zone (A-C) and in prostate cancer (D, E) at three different field strengths: 1.5 T (A, D), 3 T (B, E) and 7 T (C). Note the difference in spectral shape of citrate across the different field strengths, and the relative difference in metabolite levels between healthy peripheral zone and cancer. All spectra were acquired as part of a 3D MRSI measurement with the following effective voxel volumes (incorporating weighted k-space acquisition and filtering): 0.64 cm3 at
1.5 T, 0.37 cm3 at 3 T and 0.19 cm3 at 7 T. PZ: peripheral zone; PCa: prostate cancer; Cho: choline containing
compounds; Cr: creatine and phosphocreatine; Cit: citrate; and PA: polyamines, mainly spermine and spermidine. Collection of modified spectra from (46,49,97).
depending on whether k-space weighted acquisition and filtering has been applied (54) or not (42). At this resolution at 3 T with an endorectal coil, the SNR is not the limiting factor of the pulse sequence anymore. It is the acquisition of all steps in the weighted k-space sampling scheme that accounts for the total acquisition time, rather than multiple averaging for adequate SNR. New acquisition strategies are developed to overcome these limitations of 3 T and keep scan time short (55). For MRSI an increase in field strength is beneficial not only in terms of SNR, but also in terms of spectral resolution. The frequency dispersion between the different peaks in an MR spectrum increases linearly with field strength, whereas the line width of each peak depends on the T2* of the metabolites, reflecting the B0 homogeneity (compare Fig. 2.3A-C). Due to stronger susceptibility differences between tissues and between tissue and air or rectal gas, B0 homogeneity in and around the prostate deteriorates at higher fields. In order to make full use of the increased spectral resolution, the linewidths of the metabolites of interest in the spectra need to increase
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less than linearly with field. Currently, supervised automated shimming procedures need to be employed to optimize the local B0 homogeneity in the prostate just before the MRSI data acquisition (56). The use of an endorectal coil is often combined with an inert fluid inside the inner balloon of this coil to locally reduce susceptibility differences, resulting in reduced mean line widths of voxels in the prostate of 7.3±2.0 Hz (perfluorocarbon in endorectal coil) versus 13.3±3.0 Hz (air in endorectal coil) at 1.5 T (57).
Another aspect of moving to a higher field strength is the inter-RF-pulse timing in the 3D point-resolved spectroscopy (PRESS) sequence for prostate MRSI. This pulse timing should be optimized with regard to the shape of citrate, of which four protons form a strongly coupled spin system around 2.60 ppm, and its shape depends on the pulse timings as well as on the magnetic field strength (58,59). The resulting TE of the PRESS sequence should also be smaller than or at least of the order of the T2 relaxation time of citrate and choline to have sufficient signal left at TE. The T2 values of 0.22±0.09 s for choline, and 0.17±0.05 s for citrate at 3 T (59) do not significantly differ from the values at 1.5 T (0.23±0.06 s for choline (60), and an averaged apparent T2 value of 0.13±0.03 s for citrate in the whole prostate (61)), but they emphasize the need to choose a short TE at both field strengths. At 1.5 T the optimal TE of the PRESS was therefore determined to be ~120 ms, where the central peaks of the citrate multiplet have the highest intensity and both citrate and choline still have sufficient signal left (62). For 3 T there are several possibilities for an in-phase spectral shape of citrate; a TE of 145 ms is often chosen as it provides a maximum positive citrate shape, which without spectral line fitting is easier to interpret than the negative citrate shapes at a TE of 75 and 100 ms (56,59).
One would expect a better separation of the creatine and choline resonances at 3 T compared with 1.5 T, because of the increase in spectral resolution. However, resonances from polyamines are often present between 3.0 and 3.3 ppm (63,64), which prevents the spectrum from reaching the spectral baseline between the creatine and choline signals (53). Signal intensities of the strongly coupled molecule spermine, the most abundant polyamine (63), also vary largely with magnetic field strength and pulse timing, just like citrate (65). The exact spectral shape of spermine around 3.10 ppm with regard to pulse sequence timing and field strength needs more investigation to improve the manual or automatic analysis of the spectra. As short repetition times are often used in 3D MRSI at both 1.5 and 3 T, knowledge of T1 relaxation times of the different metabolites can be of importance for correct interpretation and absolute quantification of the spectra. The T1 of citrate increases from 0.34±0.04 s at 1.5 T to 0.47±0.14 s at 3 T, where choline was measured to have a T1 of 0.84±0.09 s at 1.5 T and 1.1±0.4 s at 3 T (59,60). In 3D PRESS MRSI of the prostate
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using weighted acquisition, the repetition time (TR) of choice to enable as many weighted acquisitions as possible in a clinically acceptable measurement time was 640 ms and 750 ms for 1.5 and 3 T, respectively (54,59). Absolute quantification of the different metabolites would be desirable, but suffers from too many uncertainties at short TR, long TE, and changing spectral shapes with the currently employed sequences. Utilizing tissue water as an internal reference and correcting for the above-mentioned factors has been attempted to obtain absolute metabolite levels of the prostate at 1.5 T (60,66), but the accuracy of the results is questionable due to the number of corrections applied and assumptions made, e.g. equal tissue water content and metabolite relaxation times throughout the whole prostate. The current quantitative marker for prostate cancer – the choline + creatine to citrate ratio – should therefore be validated for the used pulse sequence timing and field strength (46).