Optimized ¹H MRS and MRSI methods for the in vivo detection of boronophenylalanine

Abstract

Boronophenylalanine (BPA) is used as Boron-10 carrier in boron neutron capture therapy, an experimental cancer radiotherapy. Results of quantitative, noninvasive in vivo detection and imaging of BPA in laboratory animals using 1 H NMR are presented for the first time. The purpose of this study was to implement and validate optimized techniques for the efficient detection of BPA. The 1 H NMR signals through which BPA is most readily detected in vivo are those from the aromatic ring of the molecule, which are part of a scalar-coupled spin system. The preferred detection method should therefore be based on a pulse sequence in which the effective TE is as short as possible. Modified versions of LASER ( CP ‫؍‬ 4.6 ms, TE ‫؍‬ 27.6 ms) and double-echo slice-selective 2D MRSI (TE ‫؍‬ 12 ms) were implemented for single-voxel spectroscopy and spectroscopic imaging of BPA, respectively. Chemical shift selective excitation was used for both sequences, based on a pulse that enabled narrow-band excitation without concomitant delay in TE. SI data without water suppression was used for absolute quantitation and for correction of Boron neutron capture therapy (BNCT) is a binary cancer treatment, in which 10 B nuclei, preferably targeted to tumors by suitable carrier molecules, are irradiated with low-energy neutrons, causing localized short-range and cell-damaging radiation (1). One of the problems confronting successful clinical implementation of BNCT is the difficulty of quantitatively mapping the distribution of the boronated (and 10 B-enriched) molecules in patients in the course of the treatment session. So far, MR is the only modality capable of fulfilling this task. Detection of the NMR-sensitive 10 B spin is the most straightforward approach to this problem, which was shown to be feasible for BSH, another molecule used in BNCT (2). However, in boronophenylalanine (BPA) the 10 B transverse relaxation is far more rapid than in BSH, so that direct 10 B detection is at much greater disadvantage compared to 1 H detection.The possibility of detecting the aromatic BPA protons was recognized previously and demonstrated on a patient using standard STEAM (TE ϭ 30 ms) (3). Subsequent studies characterized the echo-time dependence of the aromatic proton BPA signals in aqueous solutions for STEAM and PRESS sequences (4,5). As expected, these studies demonstrated the considerable modulation of the signal due to J-coupling, causing both phasing and signal loss problems and stressing the need for efficient, short-TE sequences. Echo modulation by J-coupling can be suppressed by using very short echo times or CP-type echo trains or by timing the detection to peaks of this modulation. The latter approach is also useful for spectral editing, but for 1 H couplings with low J values, this leads to rather long echo times and signal loss from intrinsic T 2 relaxation. The use of short-TE localized MRS or SI was demonstrated for both STEAM-(6) and PRESS-based sequences (7). Sequences detecting the full Hahn spin echo have, in principle, a twofol...

Single‐Voxel 1H MR spectroscopy of cerebral nicotinamide adenine dinucleotide (NAD+) in humans at 7T using a 32‐channel volume coil

“…The pulse sequence uses a spectrally selective self‐refocused band‐selective uniform‐response pure‐phase (E‐BURP‐1) 90° pulse and 3 narrow band spatially selective refocusing Shinnar‐Le Roux (SLR) 180° pulses for localization (Figure ). The details of the excitation and refocusing pulses are given below.…”

Boron Neutron Capture Therapy

“…The possibility of using MRI for either 10 B or 11 B has been under investigation (218), and this may prove to be useful for real-time localization of boron in residual tumor prior to BNCT. Magnetic resonance spectroscopy (MRS) and magnetic resonance spectroscopic imaging (MRSI) also may be useful for monitoring the response to therapy (219). Kojimoto and Miyatake et al recently used MRS to analyze the target specificity of BPA and the effects of BNCT in a group of six patients using multivoxel proton MRS (220).…”

Boron neutron capture therapy (BNCT) in Finland: Technological and physical prospects after 20 years of experiences

“…The aromatic proton signals of BPA enable detection of the boron carrier because, with typical measurement settings (voxel size and measurement duration), normal brain metabolite signals do not overlap with them. MRS imaging (MRSI) of BPA-F with animals at high magnetic field has been studied by Bendel et al [134,135]. In addition, BPA quantification at 1.5 T and 3.0 T using 1 H MRS has been studied with phantoms [136,137].…”