Table 1.

Summary of pH measurement methods with various instruments.

Method	Sampling time Spatial resolution Agent [C]	Advantages and disadvantages	Reference
Microelectrode	Fast, sec Localized measurement No agent required	Fast; accurate if calibrated with an external buffer Limited to surface-accessible tumors; requires MRI to guide electrodes into tumors	[16–18]
Fluorescence imaging	Fast, sec 5 μm μM–nM	Sensitive; low cost; can be used during clinical fluorescence guided surgery Limited to surface-accessible tumors	[14,19–21, 25–29]
PET	10 min 2 mm nM	Fast; whole body imaging Requires radioactive isotope; coarse resolution; and limited accuracy	[22–24, 31]
1H MRS	>30 min 1mm3 mM	Simultaneous measurement of pHe and detection of metabolites Poor sensitivity; some agents are pH buffers that change tissue pHe	[34, 39, 40]
31P MRS	40 min 1cm3 mM	Can simultaneously measure pHi and pHe Requires a 31P MRI transceiver coil	[41, 43–46]
19F MRS	5 min 1cm3 μM–mM	Fast; good sensitivity Requires a 19F MRI transceiver coil	[42, 47, 49]
Hyperpolarized 13C MRS	5 sec 0.375 mm3 mM	Very fast Requires a 13C MRI transceiver coil; requires a hyperpolarizer instrument Short hyperpolarized 13C life time; Measures pHi and pHe	[48]
pH dependent T1 relaxation	<1 min 0.1 mm3 mM	Fast; high resolution Requires a cocktail of contrast agents	[50–53]
CEST MRI	~5 min μm–mm mM	Good specificity Poor sensitivity	[37]