Selective Multiple Quantum Coherence Research Articles

In-phase simultaneous spectral editing of lactate and alanine with suppression of J-coupled lipids by the modified selective multiple quantum coherence sequences

1H magnetic resonance spectroscopy (MRS) with the multiple quantum coherence (MQC) technique allows for the detection of lactate, an end product of glycolysis, in the environment of lipids. The method can also be used to detect alanine, a byproduct of glutaminolysis. An issue is that when both lactate and alanine are detected together by the MQC technique, a phase mismatch arises between lactate and alanine signals due to off-resonance rotations and the difference in double quantum coherence frequencies between the two molecules. Such phase mismatch can cause errors in spectral fitting and metabolite quantification. In this study, we designed two pulse sequences that eliminate such phase differences of lactate and alanine while suppressing lipid signals by modifications of the Selective Multiple Quantum Coherence (Sel-MQC) sequence, a well-known MQC technique. Using the product operator formalism and the off-resonance rotation matrices, the phase evolutions of lactate and alanine during the spectrally selective pulses and the free precession times of the sequence at the single quantum, double quantum and zero quantum coherence states of these molecules were calculated. The multiple quantum (MQ) evolution time t1 that can remove the phase difference of lactate and alanine at the echo was calculated and fine-tuned with experiments. The lactate and alanine signal intensities and the editing efficiencies from the two modified Sel-MQC sequences were theoretically predicted by using the product operator evolutions and compared with the experimental data. The J-coupled lipid signals were successfully suppressed by both sequences. One of the two developed sequences was applied to a human body with a phantom of lactate and alanine, which resulted in successful in-phase editing of lactate and alanine and suppression of the lipid signals from the body. The study sets an important foundation for the noninvasive detection of lactate and alanine from tumors of cancer patients.

Coherence pathway analysis of J-coupled lipids and lactate and effective suppression of lipids upon the selective multiple quantum coherence lactate editing sequence

Objective. The selective multiple quantum coherence (Sel-MQC) sequence is a magnetic resonance spectroscopy (MRS) technique used to detect lactate and suppress co-resonant lipid signals in vivo. The coherence pathways of J-coupled lipids upon the sequence, however, have not been studied, hindering a logical design of the sequence to fully attenuate lipid signals. The objective of this study is to elucidate the coherence pathways of J-coupled lipids upon the Sel-MQC sequence and find a strategy to effectively suppress lipid signals from these pathways while keeping the lactate signal. Approach. The product operator formalism was used to express the evolutions of the J-coupled spins of lipids and lactate. The transformations of the product operators by the spectrally selective pulses of the sequence were calculated by using the off-resonance rotation matrices. The coherence pathways and the conversion rates of the individual pathways were derived from them. Experiments were performed on phantoms and two human subjects at 3 T. Main results. The coherence pathways contributing to the various lipid resonance signals by the Sel-MQC sequence depending on the gradient ratios and RF pulse lengths were identified. Theoretical calculations of the signals from the determined coherence pathways and signal attenuations by gradients matched the experimental data very well. Lipid signals from fatty tissues of the subjects were successfully suppressed to the noise level by using the gradient ratio −0.8:−1:2 or 1:0.8:2. The new gradient ratios kept the lactate signal the same as with the previously used gradient ratio 0:−1:2. Significance. The study has elucidated the coherence pathways of J-coupled lipids upon the Sel-MQC sequence and demonstrated how lipid signals can be effectively suppressed while keeping lactate signals by using information from the coherence pathway analysis. The findings enable applying the Sel-MQC sequence to lactate detection in an environment of high concentrations of lipids.

Evaluation of lactate detection using selective multiple quantum coherence in phantoms and brain tumours

Lactate is a product of glucose metabolism. In tumour tissues, which exhibit enhanced glycolytic metabolism, lactate signals may be elevated, making lactate a potential useful tumour biomarker. Methods of lactate quantitation are complicated because of overlap between the lactate methyl doublet CH3 resonance and a lipid resonance at 1.3 ppm. This study presents the use of a selective homonuclear multiple quantum coherence transfer sequence (SelMQC-CSI), at 1.5 T, to better quantify lactate in the presence of lipids. Work performed on phantoms showed good lactate detection (49%) and lipid suppression (98%) efficiencies. To evaluate the method in the brain, the sequence was tested on a group of 23 patients with treated brain tumours, either glioma (N = 20) or secondary metastases in the brain (N = 3). Here it was proved to be of use in determining lactate concentrations in vivo. Lactate was clearly seen in SelMQC spectra of glioma, even in the presence of lipids, with high grade glioma (7.3 ± 1.9 mM, mean ± standard deviation) having higher concentrations than low grade glioma (1.9 ± 1.5 mM, p = 0.048). Lactate was not seen in secondary metastases in the brain. SelMQC-CSI is shown to be a useful technique for measuring lactate in tumours whose signals are otherwise contaminated by lipid. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd.

Lactate detection in inducible and orthotopic Her2/neu mammary gland tumours in mouse models

This study compared the steady state concentration of lactate in an inducible Her2/nue transgenic breast cancer mouse model and in tumours from the same Her2/neu model grown orthotopically. In vivo lactate was detected by MRS using the Hadamard encoded selective multiple quantum coherence pulse sequence (HadSelMQC) recently developed by our laboratory. A lower lactate signal was observed in the inducible tumours compared to orthotopic tumours in vivo, while ex vivo analysis of perchloric acid extracts revealed similar amounts of this metabolite in both models. Histological staining of mammary tumour specimens showed a much higher level of fat tissue in inducible tumours compared to the orthotopic model. Phantom studies with [3-(13) C] lactate indicated that a lipid environment could significantly reduce the T2 of lactate and impede its detection. The transgenic inducible model for breast cancer not only better recapitulated the biological aspects of the human disease but also provided additional characteristics related to in vivo detection of lactate that are not available in orthotopic or xenograft models. This study suggests that the level of lactate measured by the HadSelMQC pulse sequence may be underestimated in human patients in the presence of high lipid levels that are typically encountered in the breast.

The fast spiral‐SelMQC technique for in vivo MR spectroscopic imaging of polyunsaturated fatty acids in human breast tissue

The selective multiple-quantum coherence transfer method has been applied to image polyunsaturated fatty acids (PUFA) distributions in human breast tissues in vivo for cancer detection, with complete suppression of the unwanted lipid and water signals in a single scan. The Cartesian k-space mapping of PUFA in vivo using the selective multiple-quantum coherence transfer (Sel-MQC) chemical shift imaging (CSI) technique, however, requires excessive MR scan time. In this article, we report a fast Spiral-SelMQC sequence using a rapid spiral k-space sampling scheme. The Spiral-SelMQC images of PUFA distribution in human breast were acquired using two-interleaved spirals on a 3 T GE Signa magnetic resonance imaging scanner. Approximately 160-fold reduction of acquisition time was observed as compared with the corresponding selective multiple-quantum coherence transfer CSI method with an equivalent number of scans, permitting acquisition of high-resolution PUFA images in minutes. The reconstructed Spiral-SelMQC PUFA images of human breast tissues achieved a sub-millimeter resolution of 0.54 × 0.54 or 0.63 × 0.63 mm(2) /pixel for field of view = 14 or 16 cm, respectively. The Spiral-SelMQC parameters for PUFA detection were optimized in 2D selective multiple-quantum coherence transfer experiments to suppress monounsaturated fatty acids and other lipid signals. The fast in vivo Spiral-SelMQC imaging method will be applied to study human breast cancer and other human diseases in extracranial organs.

Lactate MRSI and DCE MRI as surrogate markers of prostate tumor aggressiveness

Longitudinal studies of lactate MRSI and dynamic contrast-enhanced MRI were performed at 4.7 T in two prostate tumor models grown in rats, Dunning R3327-AT (AT) and Dunning R3327-H (H), to determine the potential of lactate and the perfusion/permeability parameter Ak(ep) as markers of tumor aggressiveness. Subcutaneous AT (n = 12) and H (n = 6) tumors were studied at different volumes between 100 and 2900 mm(3) (Groups 1-5). Lactate concentration was determined using selective multiple quantum coherence MRSI with the phantom substitution method. Tumor enhancement after the administration of gadolinium diethylenetriaminepenta-acetic acid was analyzed using the Brix-Hoffmann model and the Ak(ep) parameter was used as a measure of tumor perfusion/permeability. Lactate was not detected in the smallest AT tumors (Group 1; 100-270 mm(3) ). In larger AT tumors, the lactate concentration increased from 2.8 ± 1.0 mm (Group 2; 290-700 mm(3)) to 8.4 ± 2.9 mm (Group 3; 1000-1340 mm(3)) and 8.2 ± 2.2 mm (Group 4; 1380-1750 mm(3) ), and then decreased to 5.0 ± 1.7 mm (Group 5; 1900-2500 mm(3)), and was consistently higher in the tumor core than in the rim. Lactate was not detected in any of the H tumors. The mean tumor Ak(ep) values decreased with increasing volume in both tumor types, but were significantly higher in H tumors. In AT tumors, the Ak(ep) values were significantly higher in the rim than in the core. Histological hypoxic and necrotic fractions in AT tumors increased with volume from 0% in Group 1 to about 20% and 30%, respectively, in Group 5. Minimal amounts of hypoxia and necrosis were found in H tumors of all sizes. Thus, the presence of lactate and heterogeneous perfusion/permeability are signatures of aggressive, metabolically deprived tumors.

Detection of lactate with a hadamard slice selected, selective multiple quantum coherence, chemical shift imaging sequence (HDMD‐SelMQC‐CSI) on a clinical MRI scanner: Application to tumors and muscle ischemia

Lactate is an important metabolite in normal and malignant tissues detectable by NMR spectroscopy; however, it has been difficult to clinically detect the lactate methyl resonance because it is obscured by lipid resonances. The selective homonuclear multiple quantum coherence transfer technique offers a method for distinguishing lipid and lactate resonances. We implemented a three-dimensional selective homonuclear multiple quantum coherence transfer version with Hadamard slice selection and two-dimensional phase encoding (Hadamard encoded-selective homonuclear multiple quantum coherence transfer-chemical shift imaging) on a conventional clinical MR scanner. Hadamard slice selection is explained and demonstrated in vivo. This is followed by 1-cm(3) resolution lactate imaging with detection to 5-mM concentration in 20 min on a 3-T clinical scanner. An analysis of QSel gradient duration and amplitude effects on lactate and lipid signal is presented. To demonstrate clinical feasibility, a 5-min lactate scan of a patient with a non-Hodgkin's lymphoma in the superficial thigh is reported. The elevated lactate signal coincides with the T(2)-weighted image of this tumor. As a test of selective homonuclear multiple quantum coherence transfer sensitivity, a thigh tourniquet was applied to a normal volunteer and an increase in lactate was detected immediately after tourniquet flow constriction. In conclusion, the Hadamard encoded-selective homonuclear multiple quantum coherence transfer-chemical shift imaging sequence is demonstrated on a phantom and in two lipid-rich, clinically relevant, in vivo conditions.

Sensitive J‐coupled metabolite mapping using Sel‐MQC with selective multi‐spin‐echo readout

The selective multiple quantum coherence technique is combined with a read gradient to accelerate the measurement of a specific scalar-coupled metabolite. The sensitivities of the localization using pure phase encoding and localization with the read gradient are compared in experiments at high magnetic field strength (17.6 T). Multiple spin-echoes of the selective multiple quantum coherence edited metabolite are acquired using frequency-selective refocusing of the specified molecule group. The frequency-selective refocusing does not affect the J-modulation of a coupled spin system, and the echo time is not limited to a multiple of 1/J to acquire pure in-phase or antiphase signal. The multiple echoes can be used to accelerate the metabolite imaging experiment or to measure the apparent transverse relaxation T(2). A simple phase-shifting scheme is presented, which enables the suppression of editing artifacts resulting from the multiple spin-echoes of the water resonance. The experiments are carried out on phantoms, in which lactate and polyunsaturated fatty acids are edited, and in vivo on tumors, in which lactate content and T(2) are imaged. The method is of particular interest when a fast and sensitive selective multiple quantum coherence editing is necessary, e.g., for spatial three dimensional experiments.

In vivo lactate signal enhancement using binomial spectral‐selective pulses in selective MQ coherence (SS‐SelMQC) spectroscopy

Tumor vasculature and tissue oxygen pressure can influence tumor growth, metastases, and patient survival. Elevated levels of lactate may be observed during the process of aggressive tumor development accompanied by angiogenesis (the evolution of the microenvironment). The noninvasive MR detection of lactate in tumor tissues as a potential biomarker is difficult due to the presence of co-resonating lipids that are present at high concentrations. Methods were previously reported for lactate editing using the SELective Multiple Quantum Coherence (SelMQC) method. Here we report a sequence "SS-SelMQC," Spectral-Selective SelMQC, which is a modified version of SelMQC using binomial pulses. Binomial pulses were employed in this editing sequence for frequency excitation or inversion of selective lactate resonances. Lactate detection has been demonstrated using SS-SelMQC, both in vitro (30 mM lactate/H(2)O doped with 25 microM Gd-DTPA) and in vivo (Dunning R3337-AT prostate tumors), and compared to similar measurements made with SelMQC. Lactate areas were measured from nonlocalized spectra, one-dimensional (1D) localized spectra, and two-dimensional chemical shift images (CSI) of the localized slice. In data from whole phantoms, the modified pulse sequence yielded enhancement of the lactate signal of 2.4 +/- 0.40 times compared to SelMQC. Similar in vivo lactate signal enhancement of 2.3 +/- 0.24 times was observed in 1D slice-localized experiment.

In vivo (1)H MRS of WSU-DLCL2 human non-Hodgkin's lymphoma xenografts: response to rituximab and rituximab plus CHOP.

In order to identify early (1)H MRS metabolic markers of response to rituximab immunotherapy and to rituximab plus CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine, and prednisone) combination therapy, we performed an in vivo MRS investigation of a non-Hodgkin's lymphoma (NHL) xenograft model. Human WSU-DLCL2 NHL cells were subcutaneously implanted into flanks of female severe combined immunodeficient mice. When tumor volumes reached approximately 600 mm(3), rituximab was administered for three weekly cycles at a dose of 25 mg/kg per cycle with or without CHOP. Before and after treatment, tumor lactate (Lac) and total choline (tCho) were detected using the selective multiple quantum coherence sequence and the stimulated echo acquisition mode sequence, respectively. Rituximab produced a small tumor growth delay ( approximately 5 days), whereas treatment with rituximab plus CHOP (RCHOP) led to approximately 20% tumor regression after three cycles of therapy. After one cycle of rituximab, the tCho/H(2)O ratio had decreased significantly (5%, P = 0.003), whereas the Lac/H(2)O ratio had not changed (P = 0.58). Both Lac/H(2)O and tCho/H(2)O had decreased after one cycle of RCHOP treatment (26%, P = 0.001; 10%, P = 0.016, respectively). After two cycles of RCHOP, Ki67 assay of histological tumor specimens indicated approximately 40% decrease in proliferation (P < 0.001) in the RCHOP-treated tumors; no change was detected after treatment with rituximab alone. This study suggests that decreases in tCho/H(2)O are more sensitive indices of response to rituximab, whereas decreases in Lac/H(2)O are more sensitive to response to CHOP combination therapy.

In vivo MRS markers of response to CHOP chemotherapy in the WSU-DLCL2 human diffuse large B-cell lymphoma xenograft.

To identify 1H-MRS molecular biomarkers of early clinical therapeutic response in non-Hodgkin's lymphoma, an in vivo longitudinal study was performed on human non-Hodgkin's diffuse large B-cell lymphoma xenografts (WSU-DLCL2) grown in the flanks of female SCID mice. 31P-MRS measurements, which have been demonstrated to be prognostic clinical indices of response (Arias-Mendoza et al. Acad. Radiol. 2004; 11: 368-376) but which provide lower spatial resolution, were included for comparison. The animals received CHOP (cyclophosphamide, hydroxydoxorubicin, oncovin and prednisone) chemotherapy for three 1-week cycles, resulting in stable disease based on tumor volume. Localization of total choline and phosphorus metabolites in vivo was achieved with stimulated echo acquisition mode and image selected in vivo spectroscopy sequences, respectively. Significant decreases in lactate were detected by the selective multiple quantum coherence spectral editing technique after the first cycle of CHOP, whereas total choline and the phosphomonoester/nucleoside triphosphate ratio did not change until the third cycle. Ex vivo extract MRS of tumors corroborated the in vivo results. Histological staining with antibodies to Ki67 revealed a decrease in proliferation rate in CHOP-treated tumors that coincided with the decrease in lactate. This study demonstrates the utility of lactate as an early proliferation-sensitive indicator of therapeutic response in a mouse model of non-Hodgkin's lymphoma and serves as a basis for future clinical implementation of these methods.

In vivo MR spectroscopic imaging of polyunsaturated fatty acids (PUFA) in healthy and cancerous breast tissues by selective multiple‐quantum coherence transfer (Sel‐MQC): A preliminary study

The spatial distribution of polyunsaturated fatty acids (PUFA) in healthy and cancerous human breast tissues was measured in vivo with a selective multiple-quantum coherence transfer (Sel-MQC) technique. This method selectively detected the olefinic methylene protons (-CH = CH-) of PUFA at 5.3 ppm that were coupled with allylic methylene protons (-CH(2)-CH(2)-CH=) of unsaturated acyl chain at 2.8 ppm. Unwanted lipid coherences and tissue water signal were dephased in a single scan. Breast PUFA were mapped at 1 cm(3) voxel resolution in sagittal slices of nine breasts in six healthy female volunteers that were compared to invasive ductal carcinoma (IDC) in one breast cancer patient. The healthy breast tissue displayed continuous PUFA distribution. In some individuals, PUFA appeared throughout the breast tissue; in others they were only located in the central breast area. Decreased PUFA levels were detected in the IDC of the breast cancer patient. The magnetic resonance spectroscopic imaging (MRSI) measurement was consistent with the histological findings, ultrasound, and mammography images. PUFA patterns are sensitive to abnormal breast tissue changes including malignant transformations, and thus may serve as a biomarker for early diagnosis and therapeutic monitoring of breast disease.

WE‐C‐ValB‐04: Magnetic Resonance Spectroscopy Detects Metabolic Changes Upon Chemotherapy of Human Non‐Hodgkin's Lymphoma Xenografts

A preliminary multi‐institutional study has recently demonstrated that ratios of the hosphomonoesters, phosphoethanolamine plus phosphocholine, to NTP of human non‐Hodgkin's lymphoma (NHL) easured by 31P MRS before initiation of therapy can identify about 2/3 of the patients who will not exhibit a complete local clinical response. These patients should be encouraged to undergo more aggressive alternative therapy, which entails some risk of mortality but also offers hope of response, remission or cure. However, the limited sensitivity of 31P MRS limits its application mostly to large, superficial tumors. We have, therefore, been developing much more sensitive 1H MRS and MRI methods to examine smaller tumors. Here we report studies of mouse xenografts of the most common form of human NHL and the only form that exhibits cures (in about 1/3 of the patients) — diffuse large B‐cell lymphoma (DLCL2). In vivo 1H MRS using a selective multiple quantum coherence pulse sequence (Sel‐MQC) detected decreases of lactate and total choline in DLCL2 tumors treated with three cycles of CHOP (cyclophospamide, doxorubicin, vincristine, prednisone) chemotherapy with Bryostatin added to suppress expression of the mdr1 gene. Single voxel localized spectroscopy (STEAM) detected decreases in choline and lactate/lipid that accompanied response. These changes correlated decreases in phosphomonesters detected by 31P MRS with tumor growth delay. In vivo data were correlated with data on tumor extracts. Our data suggest that 1H MRS may provide a very sensitive method for detecting early response of human NHL to chemotherapy; 1H MRI studies of response are in progress.

In vivo tumor lactate relaxation measurements by selective multiple-quantum-coherence (Sel-MQC) transfer.

The frequency-selective multiple-quantum-coherence (Sel-MQC) lactate (Lac) filter offers complete lipid and water suppression in a single scan for robust in vivo detection of tumor Lac, even in the presence of abundant lipids. Conversion of the detected signal into accurate tissue concentrations of Lac requires knowledge of in vivo Lac T1 and T2 relaxation times. This work reports modifications to the Sel-MQC pulse sequence, T1- and T2-Sel-MQC, that facilitate relaxation measurements of Lac. The T1-Sel-MQC sequence combines an inversion prepulse with the Sel-MQC filter. The T2-Sel-MQC sequence incorporates a CH3-selective 180 degrees pulse during the MQ preparation period to overcome the J-modulation effects and allow the insertion of variable echo delays. The performance of these sequences was evaluated with the use of phantoms and subcutaneous murine tumor models in vivo. The present approach will allow investigators to correct for the relaxation-induced Lac signal loss in Sel-MQC experiments for the quantitative mapping of in vivo tumor Lac distribution.

Detecting early response to cyclophosphamide treatment of RIF‐1 tumors using selective multiple quantum spectroscopy (SelMQC) and dynamic contrast enhanced imaging

The purpose of this study was to develop a reliable, noninvasive method for early detection of tumor response to therapy that would facilitate optimization of treatment regimens to the needs of the individual patient. In the present study, the effects of cyclophosphamide (Cp, a widely used alkylating agent) were monitored in a murine radiation induced fibrosarcoma (RIF-1) using in vivo (1)H NMR spectroscopy and imaging to evaluate the potential of these techniques towards early detection of treatment response. Steady-state lactate levels and Gd-DTPA uptake kinetics were measured using selective multiple quantum coherence (Sel-MQC) transfer spectroscopy and dynamic contrast enhanced imaging, respectively in RIF-1 tumors before, 24 and 72 h after 300 mg/kg of Cp administration. High-resolution (1)H NMR spectra of perchloric acid extracts of the tumor were correlated with lactate and glucose concentrations determined enzymatically. In vivo NMR experiments showed a decrease in steady-state lactate to water ratios (5.4 +/- 1.6 to 0.6 +/- 0.5, p < 0.05) and an increase in Gd-DTPA uptake kinetics following treatment response. The data indicate that decreases in lactate result from decreased glycolytic metabolism and an increase in tumor perfusion/permeability. Perchloric acid extracts confirmed the lower lactate levels seen in vivo in treated tumors and also indicated a higher glycerophosphocholine/phosphocholine (GPC/PC) integrated intensity ratio (1.39 +/- 0.09 vs 0.97 +/- 0.04, p < 0.01), indicative of increased membrane degradation following Cp treatment. Steady-state lactate levels provide metabolic information that correlates with changes in tumor physiology measured by Gd-DTPA uptake kinetics with high spatial and temporal resolution. Both of these parameters may be useful for monitoring early tumor response to therapy.

Evaluation of Lactate as a 1 H Nuclear Magnetic Resonance Spectroscopy Index for Noninvasive Prediction and Early Detection of Tumor Response to Radiation Therapy in EMT6 Tumors

In a recent study (Int. J. Radiat. Oncol. Biol. Phys. 36, 635-639, 1996), 1H nuclear magnetic resonance (NMR) spectroscopy was used to demonstrate significant decreases in lactate levels after gamma irradiation of radiosensitive RIF-1 tumors in vitro. For comparison, we have examined the effects of gamma radiation on lactate levels in the more radioresistant EMT6 tumor. Single-slice (5-6 mm thick) localized 1H spectra of subcutaneous RIF-1 (untreated) and EMT6 tumors (pretreatment, 24 and 48 h postirradiation with 4, 10 or 20 Gy of gamma radiation) were measured by the selective multiple quantum coherence transfer method (Sel-MQC, approximately 4 min acquisition time). Both pretreatment lactate levels and pretreatment lactate dehydrogenase (LDH) activities were found to be similar in RIF-1 and EMT6 tumors, suggesting that steady-state lactate levels are unlikely to be reliable indices for predicting response to radiation therapy. After 10 Gy gamma irradiation, EMT6 tumors showed a 21% decrease relative to pretreatment lactate levels at 48 h (1.04 +/- 0.22 to 0.82 +/- 0.16; P = 0.06); after 20 Gy a 40% decrease was observed at 48 h (1.34 +/- 0.27 to 0.81 +/- 0.10; P = 0.07). No significant changes in lactate levels were observed in control EMT6 tumors or in tumors treated with 4 Gy of gamma radiation, in contrast to changes detected previously in RIF-1 tumors, which showed a significant decrease in lactate by 48 h for both 2 and 4 Gy. The decreased effect of radiation on lactate levels in EMT6 compared to RIF-1 tumors may be attributed to the higher hypoxic fraction and lower radiosensitivity of EMT6 tumors (Int. J. Radiat. Oncol. Biol. Phys. 10, 695-712, 1984). The decrease in lactate levels did not, however, strictly reflect the extent of the response to therapy for the high dose of 20 Gy. This study together with our earlier study (Int. J. Radiat. Oncol. Biol. Phys. 36, 635-639, 1996) provides evidence to support the hypothesis that changes in steady-state tumor lactate levels may serve as sensitive early indices of tumor response to gamma radiation at doses of the order of 2 to 4 Gy.

Proton Detection of Choline and Lactate in EMT6 Tumors by Spin-Echo-Enhanced Selective Multiple-Quantum-Coherence Transfer

An extension of the Sel-MQC pulse sequence—SEE-SelMQC (spin-echo-enhanced selective multiple-quantum coherence transfer)—that completely suppresses lipid and water in tissues containing mobile lipid in a single scan and detects1H resonances of multiple metabolites is described. As in the Sel-MQC lactate-editing experiments [Q. Heet al., J. Magn. Reson. B106, 203 (1995)], SEE-SelMQC acquires lactate from its ZQ → DQ coherence-transfer pathway; in addition, the method recovers signal from other metabolites by selective generation of additional spin echoes using extra frequency-selective pulses and gradients. This method introduces no loss of lactate signal intensity beyond the 50% that is lost through the multiple-quantum coherence-transfer process. The spatial distributions of choline and lactate with a phantom andin vivo,in subcutaneously implanted murine EMT6 tumors, have been simultaneously mapped.

Proton NMR observation of the antineoplastic agent Iproplatin in vivo by selective multiple quantum coherence transfer (Sel-MQC).

We have noninvasively detected the proton signal of an antineoplastic agent Iproplatin in vivo by selective multiple quantum coherence transfer (Sel-MQC). Without isotopic labeling or chemical modification, the Sel-MQC method labels Iproplatin by its intrinsic proton multiple quantum coherences and, hence, differentiates the Iproplatin signal from the intensive overlapping resonances of lipid and lactate. This proton NMR method should also be applicable to study other drugs with appropriate spin coupling patterns.